Mixed Plant Viral Infections: Complementation, Interference and Their Effects, a Review

Abstract

Viral diseases are a frequent problem in the agricultural sector, causing significant economic losses, so their management is a constant challenge for producers and researchers. One of the factors that often complicates the control of viral diseases in plants is mixed infections, which occur when two or more viruses are present in a plant, generating a complex expression of symptoms. During a mixed infection, the following types of interactions basically occur: complementation and interference, the effect of which produces synergism, antagonism, or no effect. However, there are also subcategories of effects. This makes early detection difficult, and this infection can also give a competitive advantage to the pathogens involved. This review presents updated information on mixed viral infections in plants, the interaction categories, the severity of symptoms, and the impact on plants and vectors. The intention is to share information to better understand the etiology of the diseases.

1. Introduction

Plants are confronted with various pathogenic organisms, such as fungi, bacteria, and viruses, affecting their growth and development throughout their cycle. Therefore, disease and symptoms can occur continuously in the host. After infection by a viral species, plants present symptoms such as mosaicism, chlorosis, atrophy, necrosis, impaired growth and reproductive functions, growth retardation, fruit deformation, and low plant yield [1]. The problem of viral infections in plants is aggravated when two or more viruses attack a host simultaneously, since sometimes the symptoms tend to be more severe, and the disease can prevail throughout the development of the plant; this type of infection is known as mixed viral infection [2]. Mixed infections involve three actors: the plant or host, the virus, and the transmission. Viruses involved in mixed infections can be transmitted by nematodes, fungi, insects, or mechanically, as in some species of the genera Nepovirus, Tobravirus, and Tobamovirus [3,4,5]. Vectors play a specific role: infecting cultivated or wild plants, serving as a host for the coexistence of multiple viruses, and transmitting or transporting viruses in different plants, respectively, which is illustrated in Figure 1.

Viruses infect diverse wild and cultivated plant species, allowing more than one virus to coexist in the same host (plant). This circumstance can facilitate the transmission of a viral mixture between different plants, thus generating what is known as mixed infection [6]. However, viruses can mix through infections by vectors of different species that inoculate specific viruses from different hosts [7]. In viral infections, two or more plant viruses interact in different ways; sometimes, this interaction can be complementary with a synergistic effect, increasing the replication and/or movement within the plant of one of the viruses and enhancing the symptoms. When mixed viral infections generate synergistic effects that accentuate the symptoms of the disease, devastating infections occur that affect production results. An example of this is viral disease in sweet potato, which is caused by a viral infection by the sweet potato chlorotic stunt virus (SPCSV) and the sweet potato feathery mottle virus (SPFMV) [8]. In cases where interference exists, the effect is antagonism in a mixed viral infection. This can occur in two ways: cross-protection, where a previous infection prevents or interferes with a subsequent infection with another virus, or the variant of the same virus. The disease no longer significantly affects the host when the viral variant interacts. The second is mutual exclusion, where two or more viruses synchronously infect the plant [9,10]. A contemporary example of the use of cross-protection is reported in a work using attenuated variants of the cucumber mosaic virus (CMV), in which sequences from the tomato yellow leaf curl virus (TYLCV) were inserted. The generated variants conferred protection against CMV and TYLCV individually and in a mixture [10].

Mixed viral infections have been intensively studied in humans and animals [11,12,13,14,15,16,17,18]. However, there are fewer studies on mixed viral infections in plants of agricultural interest despite their beginning in the early twentieth century [19]. These studies provide evidence of the high incidence of this type of infection and the severity of the symptoms they induce in the plant. Maliogka et al. [20] point out that fruit trees are susceptible to mixed infections due to transmission through vegetative propagation and injection of infected plant material, causing severe crop losses. Despite this, detecting and characterizing the viruses causing the infection is challenging and, in some cases, complex. Skoracka et al. [21] mention that mixed infections of four viruses, wheat mosaic virus, high plains wheat mosaic virus, brome wheat mosaic virus, and Triticum mosaic virus, in wheat plants cause severe symptoms. These mixed infections cause considerable yield losses, and chemical control strategies are ineffective for disease management. On the other hand, Alcaide et al. [8] indicated that mixed infections are more than frequent, and their virus–virus interaction affects viral characteristics. The above favors the prevalence and appearance of viral diseases throughout plant development. Plants with mixed infections often go unnoticed despite presenting severe symptoms; in many cases, they can provide advantages for both viruses, favoring their dissemination and transmission by vectors [21]. Mixed infections as events require a broader perspective than analyzing a single virus or host to better understand their relevance and impact [22]. It has been reported that interactions between viruses that infect the same host are often complex. The interactions of wheat streak mosaic virus (WSMV), Triticum mosaic virus (TriMV), brome mosaic virus (BMV), and barley streak mosaic virus (BSMV), evaluated in wheat fields, resulted in a very severe disease synergism, causing death in most of the plants but a reduction in the viral concentration of BSMV [23]. Considering the above, this review aims to reinforce the notion that there are only two types of interaction between viruses: complementation and interference, whose effects, in turn, are synergism or antagonism but with different characteristics according to the complementation or interference mechanism that occurs, which recurs in the expression of symptoms and impact on plants. Finally, some treatment alternatives for mixed infections are proposed.

2. Types of Interactions in Viral Infections in Plants

Mixed infections occur naturally and are frequent in cultivated native species [8,23]. As previously noted, mixed infections between two or more viruses are characterized by their complex interaction; in most cases, this interaction induces greater severity and incidence in the host (plant) and influences the prevalence and occurrence of diseases [24]. In the course of a mixed infection in a plant, these three situations can occur: Interaction between viruses through a complementation event, interaction between viruses through an interference event, or a situation in which there is no interaction event between the viruses despite sharing the same host. These interactions have commonly been described by their effect as synergism, antagonism, and neutralism, and these effects of interactions between viruses have a direct impact on the host plant and the relationship with the vector organisms [22], which are described below.

2.1. Complementation

In general, complementation consists of the contribution of a missing or additional capacity to a biological system or entity, in this case, a virus. The contribution of this capacity to natural conditions can be seen in trans. Another virus or other viruses provide it when there is an interaction between viruses or another biological entity in other cases. Natural or laboratory insertion of genetic sequences into viral genomes also conferred this capacity via cis-complementation. Thus, complementation in a mixed viral infection has been previously defined as an interaction in which the lack of one or more functions of a virus is provided via trans-complementation by another virus or other viruses involved, in this case, between viruses involved in a mixed infection in the same plant, tissue, or host cell. It is important to note that we are expanding and modifying, in part, previous definitions [25,26] that had been previously proposed. Different viral traits or variables can be synergized by complementation, either in cis-complementation or in trans-complementation. These include high viral titers, movement, altered cell or tissue tropism, host range expansion [27], increased transmission, and increased specific infectivity. Complementation occurs through proteins such as gene silencing inhibitors, replicases, capsid proteins, movement proteins, or nucleotide sequences. Viral complementation usually occurs between closely related viruses, although it can occur between phylogenetically divergent viruses. Depending on the circumstances, more than one function can be complemented in this type of interaction [28,29,30]. The most apparent effect of complementation as an interaction between viruses in the same host is synergism. However, neutralism can also occur; both topics will be discussed below.

2.1.1. Synergy

In synergistic interaction, one or more viruses are favored by the presence of other viruses. As mentioned, synergism manifests in an increase in viral titers and movement of altered cells, altered tissue tropism, and host range expansion, manifesting in an increase in pathogenicity, and the expression of symptoms is usually more severe ([31,32,33,34], Figure 2). A synergism is the mere presence of a specific virus in a cell, tissue, or host where the virus is not commonly found. In any case, only one of the viruses is enhanced, or the event is reciprocal. In addition, a relevant aspect of viral synergism is the increase in the capacity of movement, the transmission of at least one virus, and the suppression of plant defenses based on silencing RNA with viral proteins by the virus, which favors its replication [35,36]. Viral movement proteins (MPs) confer to viruses the ability to transport their genome from cell to cell through plasmodesmata, including to neighboring cells in plant tissues [37]. Complementation occurs between related viruses and genetically unrelated viruses, including viruses with different numbers of MPs involved [38] and even different mechanisms [39]. See Morozov & Solovyev [40] for more details on this subject. The synergistic interaction is verifiable from the appearance of symptoms; the assessment can be qualitative or quantitative and determines that not only the effects of each virus and its viral concentration are observed but that in at least one relevant variable, the sum of the values of the variable of each virus involved is exceeded. Of course, these effects of viruses that behave synergistically in one case vary in others depending on the viral combinations, viral strains, and the collaboration or not of subviral agents [41], in addition to that of the host species and also the host cultivar [42]. It must be taken into account that viruses are ultimately part of a de facto microbiome at a given time, and virulent expression can also be influenced by detection signals such as quorum sensing, exoenzymes, and effectors [43]. Interestingly, it has been reported that multiple infections can occur simultaneously in the same culture in which both antagonistic and synergistic interactions are generated [6]. There are subtypes of interaction in synergistic interactions, which we mention below; only the most relevant ones.

Helper Dependence

A helper-dependent virus is not capable of replicating itself, so to do so, it depends on the genetic expression of another virus to have offspring capable of infecting it [44]. However, this interaction mechanism has also been observed regarding encapsulation of some of the viruses involved. For example, cauliflower mosaic virus (CaMV) and carrot mottle virus depend on viruses of the Luteoviridae family for encapsulation [44]. A detailed example of synergism mediated by the helper dependency mechanism is that which occurs with the coinfection of potato virus X (PVX) with one of the members of the potyvirus group, which generates an interaction that manifests itself in an increase in the severity of the disease, which is correlated with an accumulation of PVX 3- to 10-fold in infected leaves [45,46]. This is possible thanks to the helper component proteinase (HCPro), which is generated in the coding region of Potyvirus P3 and is a polyfunctional protein that acts as a potent suppressor of genetic silencing, which is, in turn, an antiviral strategy [47]. This last condition was believed to confer the ability to enable synergistic interactions with other viruses. A mutation of HCPro suggests that its ability to promote virion accumulation does not depend on its role in silencing suppression [48]. However, HCPro has other functions in cooperation with other viral and host proteins, such as virion formation, systemic movement, and virus transmission by aphids [47].

Overcoming Cell and Tissue Tropism

Viral tropism is the specificity of a virus to infect only some types of cells or tissues and be able to enter others [49,50]. This condition can be modified in mixed viral infections when two or more viruses share the same host, tissue, or cell. The results under these conditions can be unpredictable, but one effect that can occur is the alteration or change of viral tropism [50]. The plant’s developmental stage sometimes determines the type of interaction that can occur. In this sense, the change from antagonism to synergy between unrelated virus species located in different tissues has been reported. An example is that in which the switch from antagonism to synergy was described in tomatoes between the begomoviruses tomato rugose mosaic virus (ToRMV) and tomato yellow spot virus (ToYSV) [51]. ToRMV antagonized ToYSV in the early stages of infection, but when systemic infection was achieved, the antagonism ceased, and ToYSV helped ToRMV establish a systemic infection as well. Synergism due to alterations in viral tropism has also been reported between cucumber mosaic virus (CMV), an RNA virus, and abutilon mosaic virus (AbMV), a DNA virus of tobacco and tomato. In this case, the AbMV normally bound to phloem cells was also replicated in non-vascular cells, an effect attributed to the CMV 2b protein and not to the CMV movement protein [52]. This type of synergy has also been documented by other authors, for example, in natural mixed infections of beans with bean golden mosaic virus (BGMV) with any tobamovirus [53] and also in mixed infections of PVA and PLRV in N. benthamiana plants [53,54], or natural hosts such as zucchini co-infected with ZYMV that helped CMV in its systemic spread [55]; these cases were recently mentioned by Singhal et al. [6].

Host Range Extension

This type of interaction is observed when a restrictive host for a virus species stops being so under conditions of mixed infection with another for which the host is not restrictive. Such is the phenomenon observed in the following condition: cowpea (Vigna unguiculata) is a permissive host for the southern cowpea mosaic virus (SCPMV), and the common bean (Phaseolus vulgaris) is permissive to the southern bean mosaic virus (SBMV). The cowpea is not permissive to SBMV. The bean is not permissive to SCPMV. SCPMV RNA can be synthesized in the bean, but the virus is not assembled because it is inferred that the restriction on SCPMV is because its movement is restricted in addition to its assembly. However, it has been reported that complete SCPMV is produced in bean plants’ inoculated and systemic leaves after co-inoculation with SBMV. Likewise, it has been noted that cowpea protoplasts are permissive for synthesizing and assembling SBMV RNA [5,29,34,56].

2.2. Interference

In the strictest sense, interference is any action that hinders or obstructs a process or event and whose result is a negative effect on the variable or variables that characterize the process or event in its normal development or execution. Since 1951, Bennett [57] defined interference, differentiating it from the effect, as a ‘phenomenon in which a plant or part of a plant, after being invaded by a virus or strain of virus, becomes immune or resistant to infection or invasion by a second virus or strain of the challenging virus.‘ He also mentions that there may be different types of interference between viruses, such as that which could occur, he pointed out, between unrelated viruses, a situation derived from a report by Bawden and Kassanis in 1945 [58].

Although he also called interference a phenomenon of interaction that led to synergy, here, for compatibility with the definition we propose, we will refer to his first definition as interference. Several interference mechanisms have been reported, some inferred and others arising from experimental evidence. Briefly, these are the proposals.

1. In mixed infection, the second virus is inhibited because the massive multiplication of the first virus has already occupied the receptor sites.

2. Interference can occur due to acute resource depletion because the first virus in the mixture may have exhausted one or more essential materials for the multiplication of the second virus [59].

3. The changes provoked in the plant’s metabolism can increase its resistance to infection by another virus. That is, the first virus elicits it, and therefore, inoculation with the second virus no longer achieves infection.

4. In the case of variants of the same virus species, interference may be due to the contribution of a defective protein to the replication complex of one of the variants [60].

5. More recently, it has been pointed out that one form of interference is that the first inoculated virus prevents the uncapping of the second and consequently prevents it from replicating [6,61].

6. Interference dsRNA can be derived from viral sequences even when applied directly to leaf cells, by mechanical inoculation or by means of an agrobacterium-mediated transient expression assay [62].

7. Homology-dependent viral RNA interference can be caused by RNAi and/or RNA-directed DNA methylation (RdDM) to target RNA and DNA viruses [63].

2.2.1. Antagonism

Antagonism is opposition, rejection, or rivalry between objects or subjects during an event or process, resulting in decreased values of the variables characteristic of said event or process.

In the context of a mixed viral infection, it can be defined as an event in which at least one of the viruses involved is affected in variables of interest, for example, in the expression of symptoms or the viral titer [64].

It is necessary to consider that antagonism is highly influenced by different conditions, such as the species in which the mixed infection occurs [65] and the synchrony of inoculation. If inoculation is simultaneous, it is called co-infection, and the effects of the interaction between the viruses can differ from those observed if the infection occurs at different times, in which case it is a superinfection [66].

The specific characteristics of antagonism can be identified by the different events described below:

Cross-Protection

Cross-protection occurs when host plants are first infected with an attenuated strain of a virus species and are often protected against subsequent infections by more severe strains of the same virus species. Eventually, protection can be generated with other phylogenetically related virus species, but the host remains susceptible to infection with phylogenetically more distant viruses. McKinney documented this phenomenon in 1929 [19], and it has since been used to successfully control several viral diseases of crop plants [67,68]. Although there is no consensus on the mechanism of cross-protection, it is generally accepted that a similar superinfection exclusion (SIE) effect can be induced with symptomatic virus strains, provided that the primary and superinfecting viruses are genetically related [69]. Cross-protection is a competitive interaction between viruses, called ‘superinfection exclusion’ or ‘homologous interference’, in which a previous viral infection with a protective virus interferes with the previous infection of homologous viruses [70]. Protective and homologous viruses replicate independently and move from one cell to another over long distances. However, after infection with the protective virus, the host plant develops resistance to superinfection [71]. Superinfection exclusion benefits newly created viral variants by allowing them entry into uninfected host cells relative to previously infected ones and promoting virus replication. Accordingly, it is speculated that this process plays an essential role in maintaining the genetic diversity of a viral population [72]. Superinfection exclusion may benefit a newly produced viral variant by favoring its entry into uninfected host cells rather than previously infected host cells, promoting virus dissemination. Furthermore, a primary virus that successfully infects a cell would be protected from a superinfecting competitor virus. Superinfection exclusion plays an important role in maintaining the genetic diversity of a virus population because it allows for the replication of variants that vary in fitness [73].

Mutual Exclusion

In mutual exclusion (termed ‘mutual suppression’ or ‘mutual competitive suppression’), the infection of two or more viruses in a plant occurs in parallel. For this event to occur, it is an indispensable condition that two or more viruses must infect the same host simultaneously. When it was first reported with viruses, in this case with three strains of barley yellow dwarf virus (BYDV), mild symptoms were reported in hosts shortly after infection, the plant recovered, and no virus could be detected in these plants [74]. Subsequently, evidence of this phenomenon has accumulated for different virus species and hosts, for example, with Potyvirus variants in N. benthamiana [75], with different strains of Cucumovirus (CMV) in cowpea, with apple latent spherical virus (ALSV) inoculated into Chenopodium quinoa plants, and with bean yellow mosaic virus (BYMV) inoculated into N. benthamiana [76,77]. However, the mechanism of infection is unknown since the cells are separated inside the plant, and even though two or more viruses cause disease, the plant cells are infected by only one virus [10]. When spatial separation occurs, the competition options between viral variants are reduced, which interferes with the elimination of unfit variants, increasing the general fitness of the viral population [73]. In addition to the above, spatial distribution and mutual exclusion reduce recombination and the generation of genetic variation [78,79].

The mechanism of mutual exclusion is still obscure. However, a plant could be considered a spatially structured environment for plant virus infections. Cells might only be infected by a single virus [80], which is a mechanism that appears to be valid, at least in Potyvirus [10]. Both the repeated results and the analysis of the information have strengthened the proposal of the BIAS hypothesis (bottleneck, isolate, amplify, select), which states, in summary, that at least (+) RNA viruses limit the number of replicable genomes per cell, using what is called a bottleneck to prevent their replication, in such a way that stochastically only a few managed to do so. A few escaped viral genomes that are isolated from each other in separate cells and in these bottle isolated genomes where the viral genomes that can establish and multiply are selected [81,82,83].

Competitive Suppression

This event can be an indirect interaction between viral strains and species. This phenomenon has been reported as the process of resistance to a severe infection caused by a virus that induces symptoms as a result of the action of an interfering virus that suppresses the replication of the subsequent virus, which results in an effect on its pathogenesis. The above explains why viral infection generates changes, including metabolism in the photosynthetic apparatus [34,84]. This could be possible by inducing plant resistance mechanisms that include RNA silencing, generally requiring ATP, NADPH, and structural carbon products of metabolism [85]. Photosynthesis is the main energy source, and carbon supports plant defenses against infections [46,47]. Considering that reactive oxygen species (ROS) are produced in chloroplasts during redox reactions, especially on the PSII and PSI acceptor sides [86,87] in parallel with the ROS of NADPH oxidase, they may be related to the induction of the immune response (RH), which is one of the defense mechanisms against viral infection. According to the above, photosynthesis is of great importance to the antiviral defense mechanisms of plants [85]. It has been reported that interference with chlorophyll metabolism reduces photosynthesis performance. Consequently, it has been reported that drastic reductions in chlorophyll levels during this process are associated with developing symptoms [88,89]. For example, in cowpea (Vigna unguiculata), plants infected with cowpea severe mosaic virus (CPSMV-genus Comovirus) showed a reduction of 32% and 40% in chlorophyll b content, compared to uninfected plants [90].

Tolerance

Tolerance is an interaction in which viruses accumulate in the host to a point where growth, performance, and reproductive attributes are unaffected. However, a significant viral load is maintained, and visible symptoms are absent or mild [91]. Viruses are obligate intracellular parasites; they require resources from the host to complete their infection cycle; in a tolerant interaction, the action of the virus is reduced to minimize the accumulation of viral RNA, and the concentration or activity of viral proteins that play a role in virulence, which limits damage to the host [28]. This balance is associated with little selective pressure for the emergence of severe viral strains, is common in wild ecosystems, and has important implications for managing viral diseases [92]; this may be possible because tolerant viral strains can induce plant defense and because tolerant plants can accumulate viral nucleic acid without significant damage. It is suggested that the tolerance interaction is possible due to the early activation of mechanisms observed in different plants, such as the attenuated expression of response genes like PR-1 and PR2 in tobacco plants [93], the early induction in tomato, of photosynthesis genes that are transiently induced in the early stages of viral infection and then repressed when virus multiplication begins, the dynamic regulation of secondary miRNAs and sRNAs is associated with late defense responses or a recovery phenotype in tomato that is associated with tolerance [94], all these mechanisms help to promote the tolerance response by the host against viral infection.

High Antagonism and Low Synergism

This type of interaction occurs due to variations in the duration of the period between viral inoculation, the onset of symptoms (latency period), and their severity, which suggests different levels of virus adaptation as a result of interactions between viral proteins and the host. We assume that a better-adapted virus can replicate at a higher speed and move between cells to reach other tissues, in addition to the phloem where the vector introduces the virus [95,96]. This type of interaction occurs due to variations in the duration of the period between viral inoculation, the onset of symptoms (latency period), and their severity, which suggests different levels of virus adaptation as a result of interactions between viral proteins and the host. This type of interaction occurs due to variations in the duration of the period between viral inoculation, the onset of symptoms (latency period), and their severity, which suggests different levels of virus adaptation as a result of interactions between viral proteins and the host [86]. They assume that a better-adapted virus can replicate at a higher speed and move between cells to reach other tissues, in addition to the phloem where the vector introduces the virus [95,96].

3. Symptoms in Mixed Viral Infections

The expression of symptoms in the plant varies depending on the type of mixed infection; each interaction results in a synergism, antagonism, or no effect on the symptoms in the host [6], as seen in Figure 3. The main studies of mixed infections in the most studied native and cultivable species are described below:

3.1. Symptoms in Synergy and Subtypes

3.1.1. Synergy

As an example of synergism, mixed infection with the pepper golden mosaic virus (PepGMV) and pepper huasteco yellow streak virus (PHYVV) was studied in Anaheim chili pepper plants from Sonora. Plants infected with the viral mixture presented more severe symptoms than those induced in simple viral infections. There was no remission of symptoms, and the DNA concentration of both viruses increased significantly. In the case of single infections with either virus, a remission phase was reported with a corresponding decrease in viral DNA levels. Infections with PHYVV (A + B) + PepGMV A produced a similar effect to inoculation with both complete viruses, suggesting that the viral component A of PepGMV is relevant for the synergy between the two viruses [24]. Another similar example was reported in the case of mixed infection with tomato chloro-sis virus (ToCV) and tomato yellow leaf curl virus (TYLCV). The effect was an increase in disease severity, including decreased stem height and weight during the development of the syndrome. It was also reported that the accumulation of the viruses (ToCV + TYLCV) was higher than in individually infected plants [55].

Helper Dependence

Peanut rosette disease caused by the interaction of peanut rosette virus (GRV) and peanut rosette helper virus (GRAV) is characterized by its dependence on the GRAV coat protein for packaging and transmission by aphid vectors. This is because Umbraviruses lack the genetic information to encode the coat protein. This dependence is called transencapsidation or genome masking [97]. Another example is the mixed infection of potato spindle tuber viroid (PSTVd), which is mechanically transmitted and depends on the capsid of potato leafroll virus (PLRV) for transmission and movement. This allows for the replication of Poliovirus and causes severe symptoms [98,99]. A similar case is that of barley yellow dwarf virus (BYDV) and cereal yellow dwarf virus (CYDV). BYDV RNA is encapsulated in CYDV capsids, allowing for transmission by the stem aphid (Rhopalosiphum padi L) in mixed infections of barley, oat, and wheat crops [100,101].

Overcoming Tissue Tropism

This type of interaction is visible in the case of tomato yellow spot virus (TYSV), which is found in the mesophyll cells, and tomato rough mosaic virus (ToRMV), which is found in the phloem. When it occurs, mixed infection of tomato plants by the two viruses results in the ability of ToRMV to invade the mesophyll cells together with the phloem, which this virus cannot do if it infects the plant individually [6]. This type of interaction has been observed in the southern cowpea mosaic virus (SCPMV), characterized by only infecting cowpeas. However, mixed infection with the southern bean mosaic virus (SBMV) also systematically infects common beans, which may be due to heterologous encapsidation or genome masking [22]. A synergistic effect is characterized by favoring one or all of the viral partners, manifested by increased virus replication, symptomatology, cell tropism, movement within the host, and interaction rate.

3.2. Symptoms of Antagonism and Subtypes

The expression of antagonistic symptoms has been reported based on the interaction subtypes described below.

3.2.1. Cross Protection

In a variant of the papaya ringspot virus (PRSV), cross-protection induced by the action of nitrous acid was observed, which provided adequate protection against severe PRSV isolates in geographic areas where the protective variant originated and failure against the most severe strains of the virus [102,103]. On the other hand, the citrus tristeza virus (CTV) used a recombinant virus variant marked with fluorescent protein from the T36 strain, which could not over-infect plants previously infected with variants of the same strain. However, it can infect plant carriers of other CTV strains [68,104].

3.2.2. Mutual Exclusion

In tomato plants, the effect of mixed infections with southern tomato virus (STV), cucumber mosaic virus (CMV), and pepino mosaic virus (PepMV) was studied. Co-infection with CMV and PepMV showed a substantial decrease in CMV titer and modification of plant symptoms in relation to individual infections [10]. On the other hand, co-infection with STV + PepMV + CMV restored CMV viral titer and plant symptoms. It is suggested that this could be because miRNAs in tomato plants varied the regulation of its functions and their number and level of expression, depending on the combination of viruses [10].

3.2.3. High Antagonism and Low Synergism

In mixed infections, cases of low synergism and high antagonism are reported in tomato plants infected with tomato torrado virus (ToTV) and pepino mosaic virus (PepMV). In this case, an increase in ToTV virus titers in the early stages of infection is associated with synergism. However, PepMV viral titers decreased dramatically at all-time points, suggesting antagonism [10,105].

3.3. Symptoms of Competitive Suppression or Interference

As for plants, this mechanism is not known naturally, but in vitro studies have been carried out that indicate that regarding viral interference, systems such as CRISPR/Cas 13a are used, which is an RNA effector that provides protection against viral RNA phages. The use of this technique in the protection of potato plants is reported against potato virus Y (PVY), which showed a reduced viral accumulation, as well as symptoms of the disease [106,107]. In tobacco plants, the CRISPR-Cas13 technique was used against the potato chimeric virus X, which expresses GFP (PVX-GFP), and tobacco mosaic virus, an RNA-based overexpression vector (TRBO-BFP) was used in specific crRNA sheets; an interference was observed against TRBO-BFP virus only, while PVX-GFP increased its viral load [108]. Other reported examples of using the CRISPR/Cas13a system are in tobacco plants against the tobacco mosaic virus (TMV), which resulted in viral interference of the virus [109]. It is important to emphasize that this type of technology is constantly being evaluated so that in the future, it can be used successfully to interfere with RNA viruses in plants and eukaryotic cells. Alternatively, interactions that occur through co-infection between populations of strains and virus species within the same host may result in competitiveness that suppresses or favors the survival and evolution of a specific viral genotype or phenotype due to the action of the environment. It is important to note that the environment’s most relevant and direct components for viruses are the hosts [110] and the vectors [111]. The competitive capacity for the survival of a strain or a virus will be determined by its adaptability, which is defined by the genotype or the phenotypic plasticity [112]. In the case of the genotype, the competitive advantage or disadvantage can be a bit random since it can be the product of a mutation that can enhance the adaptability of the virus by broadening the range of hosts and vector diversity or reduce it in case or generating the opposite [113]. For example, suppose a deactivation is generated in the regions of the VPg protein of the potato virus Y (PVY), which is involved in the specificity of the interactions with the genotypes of the host plant. In that case, it increases the capacity to break the resistance of Capsicum annuum to infection [114].

4. Impact of Mixed Infections

The losses caused by viral infections, whether simple or mixed, in plants are significant. It would not be easy to separate the impact of each on a global scale. However, due to the topic’s focus, emphasis will be placed on mixed viral infections. As a result of mixed infections, various impacts are caused in the host (plant), among which the increase in symptoms, reduction in yield, greater gene expression, and abrupt physiological changes reflected in metabolic modifications stand out [115]. In tobacco plants, altered gene expression was observed as a result of infection with potato virus X (PVX) and potato virus Y (PVY); this resulted in negative regulation of the gene in charge of the functioning of the chloroplast, a more significant peroxidation of lipids and superoxide radicals was reflected in the necrosis in leaves and the death of the plant [116,117]. Conversely, when infected by multiple viruses in synergistic interactions, plants present a response through RNA silencing and post-transcriptional gene silencing (PTGS) through processes such as chromatin modification and DNA methylation as a defense response to viral infection [118,119]. Finally, in mixed infections, resistance is broken in the plant due to the transformation of a host plant into a non-host plant, which facilitates the increase of possible hosts for viruses in mixed infections [120]. This is observed in a plant that was naturally resistant to a particular virus; as a result of the mixed infection, this resistance is lost, facilitating the entry of new viruses into the plant to which it was resistant before infection. Tolerance to extreme environmental conditions has been demonstrated in mixed infections with cucumber mosaic virus (CMV), tobacco mosaic virus (TMV), and tobacco rattlesnake virus (TRV) [121]. In the plants inoculated with the viruses, an increase in metabolites such as osmoprotectants and antioxidants associated with tolerance to drought and low temperatures was observed [122]. On the other hand, mixed infections facilitate the exchange of genetic material and sexual reproduction between co-infecting pathogens; this is reflected in greater virulence, the competitive capacity of the predominant virus, and, therefore, more severe symptoms. As for vectors, mixed infections influence changes in the behavior and physiology of the vector due to the variations that occur in the host or plant; these alterations condition the spread, recombination events, transcapsidation, epidemiology of the virus, and manipulation of the vector. As a result, it makes it easier for some viruses to infect hosts other than those they usually infect [6]. In mixed infections, some viruses gain the ability to be transmitted by vectors other than natural vectors when infection by a single virus occurs. This phenomenon is called genomic masking or transcapsidation, consisting of the viral genome encapsulated by the capsids of another virus present in the plant, originating a new chimeric entity with shared properties. Another impact that occurs in vectors during mixed infection is heteroencapsidation, in which the genome of one virus indefinitely acquires particles from another virus through heterologous encapsidation [123]. It has been reported that in begomoviruses transmitted by whitefly (Bemisia tabaci) frequently occur, genetic recombination during mixed infections, which gives the viruses new genetic combinations and variability of infection to a wide number of begomovirus hosts (plants).

5. Detection and Management of Mixed Viral Infections

Due to their high incidence, conventional and new instruments in plant virology should be oriented toward the early detection and management of the syndrome caused by mixed infections in plants and crops. Figure 4 shows some proposed alternatives for management and detection, which are described later.

Detection is a crucial component in managing viral diseases; various methods are available for this, such as polymerase chain reaction (PCR), real-time PCR, multiplex PCR, and non-isotopic molecular hybridization techniques. Using these methods allows the identification and characterization of the structure of the virus population; thus, management strategies are adopted that target the vector or the start of the viral infection, avoiding losses in the crop [124].

Regarding conventional management, mechanisms are proposed, such as interference with the vector using systemic insecticides such as dinotefuran, imidacloprid, thiamethoxam and cyantraniliprole [125], to reduce the spread of the virus. Essential practices are the use of virus-resistant varieties, the elimination of infected plants, and the use of virus-free plants. Finally, the elimination of alternative hosts includes practices such as destroying residues from the previous harvest, pruning, removal, and destruction of infested organs and use of trap plants, and destruction of pupae in the soil with the help of plowing [126]. The new approach to managing the syndrome, using nanoparticles (NP), is proposed given the small particle size, high surface area, and specific mechanisms such as damage to the capsid and interference with viral replication and movement [127,128]. Hydrogen peroxide is recommended because it controls and regulates biological processes, such as growth, cell cycle, programmed cell death, hormonal signaling, and responses to biotic/abiotic stress and development [129]. Genome editing has opened a great avenue to manipulate nucleic acids. CRISPR-Cas9 is a genome editing system using a laboratory tool that allows the DNA of a cell to be modified in a targeted manner at a specific site. Through the proper design of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) systems, resistance to plant viruses can be generated either by directly targeting the viral genome and/or by inactivating host susceptibility genes [130,131].

6. Conclusions

Mixed viral infections are present in different populations and may have significant but unpredictable biological and epidemiological consequences. These infections can be acquired simultaneously (coinfection) or from two single infections at different time intervals (superinfection). Therefore, knowledge of their ecology and epidemiology in plant virology is the first step to understanding their impact and interactions; this knowledge can be a starting point for the detection, diagnosis, and establishment of mechanisms that allow for reducing the severity of the disease or syndrome that mixed infection induces.

Author Contributions

M.R.S.-T. prepared the first draft, R.F.R.-B. supervised the development of the topic, D.L.S.-T. contributed to the revision of concepts, R.G.G.-G. reviewed the different drafts of the article, and I.T.-P. coordinated the structuring of the work, reviewed it, and prepared the final version. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

The authors thank the National Council of Science and Technology CONACYT, for support in resources for research, development of projects, and granting of the M.R.S.-T. postgraduate scholarship, and I.T.-P. thanks for the support for the project CB217-218 A1-S-33677.

Conflicts of Interest

The authors declare no conflict of interest.

Footnotes

Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Figures

Figure 1. This figure illustrates the following: on the left side are presented the different events under which a viral infection can occur in the same plant: (a) By virus species involved: a single virus per event, or two or more viruses per event, (b) Different moments of infection; (i) Just once or (ii) two or more times. On the other hand, infections can be caused by (a) different viruses in a single cell or different cells and (b) different viruses in the same plant tissue or different viruses in different tissues. Regarding vectors, a vector can (a) inoculate different viruses simultaneously or (b) only one at a time. The elements represent viral particles of different viruses.

Figure 2. This scheme illustrates four possible forms of synergism in mixed plant virus infections. In (A), helper dependency, a virus alone cannot replicate or move, but by combining with another virus that complements the missing function, it multiplies and moves. In (B), a virus alone is confined to only one cell type, but complementary interaction with another virus can invade other cells. In (C), the same thing happens as in the previous case but with tissues, and in (D), under the complementation scheme, the range of the virus’s hosts is extended.

Figure 3. Diagram illustrating the elements describing plants’ most common mixed viral infection events. There are only two types of interaction with different mechanisms and four of the main effects. The diagram only considers the synergistic and complementary interactions that can occur, under certain conditions, in the same host throughout its development.

Figure 4. Conventional and new practices in plant virology for managing mixed viral infections.

References

1. Mehetre, G.T.; Leo, V.V.; Singh, G.; Sorokan, A.; Maksimov, I.; Yadav, M.K.; Upadhyaya, K.; Hashem, A.; Alsaleh, A.N.; Dawoud, T.M. et al. Current developments and challenges in plant viral diagnostics: A systematic review. Viruses; 2021; 13, 412. [DOI: https://dx.doi.org/10.3390/v13030412] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33807625]

2. Rubio, L.; Galipienso, L.; Ferriol, I. Detection of plant viruses and disease management: Relevance of genetic diversity and evolution. Front. Plant Sci.; 2020; 11, 1092. [DOI: https://dx.doi.org/10.3389/fpls.2020.01092] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32765569]

3. Rao, Y.D.; Kumar, D.; Sharma, S. A comprehensive review on transmission mechanism of plant viruses by insects. Int. J. Res. Agron.; 2024; 7, pp. 337-344. [DOI: https://dx.doi.org/10.33545/2618060X.2024.v7.i7Se.1049]

4. Syller, J. Biological and molecular events associated with simultaneous transmission of plant viruses by invertebrate and fungal vectors. Mol. Plant Pathol.; 2014; 15, pp. 417-426. [DOI: https://dx.doi.org/10.1111/mpp.12101]

5. Fidan, H.; Çelik, S.; Koç, G. Virus diseases limiting greenhouses and open field production of cucurbits in Antalya province. Mediterr. Agric. Sci.; 2024; 37, pp. 57-65. [DOI: https://dx.doi.org/10.29136/mediterranean.1454954]

6. Singhal, P.; Nabi, S.U.; Yadav, M.K.; Dubey, A. Mixed infection of plant viruses: Diagnostics, interactions and impact on host. J. Plant Dis. Prot.; 2021; 128, pp. 353-368. [DOI: https://dx.doi.org/10.1007/s41348-020-00384-0]

7. Andret-Link, P.; Fuchs, M. Transmission specificity of plant viruses by vectors. J. Plant Pathol.; 2005; 87, pp. 153-165.

8. Alcaide, C.; Rabadán, M.P.; Moreno-Perez, M.G.; Gómez, P. Implications of mixed viral infections on plant disease ecology and evolution. Adv. Virus Res.; 2020; 106, pp. 145-169.

9. Zhang, X.F.; Qu, F. Cross protection of plant viruses: Recent developments and mechanistic implications. Current Research Topics in Plant Virology; Springer: Cham, Switzerland, 2016; pp. 241-250.

10. González, L.; Peiró, R.; Rubio, L.; Galipienso, L. Persistent southern tomato virus (STV) interacts with cucumber mosaic and/or pepino mosaic virus in mixed-infections modifying plant symptoms, viral titer and small RNA accumulation. Microorganisms; 2021; 9, 689. [DOI: https://dx.doi.org/10.3390/microorganisms9040689]

11. Zhu, M.; Liu, S.; Wang, Z.; Yu, C.; Yuan, X. A New Strategy of Cross-Protection Based on Attenuated Vaccines: RNA Viruses Are Used as Vectors to Control DNA Viruses. Agronomy; 2023; 13, 2334. [DOI: https://dx.doi.org/10.3390/agronomy13092334]

12. Bello, M.B.; Yusoff, K.; Ideris, A.; Hair-Bejo, M.; Peeters, B.P.; Omar, A.R. Diagnostic and vaccination approaches for Newcastle disease virus in poultry: The current and emerging perspectives. BioMed Res. Int.; 2018; 2018, 7278459. [DOI: https://dx.doi.org/10.1155/2018/7278459] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30175140]

13. Dandachi, D.; Rodriguez-Barradas, M.C. Viral pneumonia: Etiologies and treatment. J. Investig. Med.; 2018; 66, pp. 957-965. [DOI: https://dx.doi.org/10.1136/jim-2018-000712] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29680828]

14. Kumar, N.; Sharma, S.; Barua, S.; Tripathi, B.N.; Rouse, B.T. Virological and immunological outcomes of coinfections. Clin. Microbiol. Rev.; 2018; 31, e00111-17. [DOI: https://dx.doi.org/10.1128/CMR.00111-17]

15. Murin, C.D.; Wilson, I.A.; Ward, A.B. Antibody responses to viral infections: A structural perspective across three different enveloped viruses. Nat. Microbiol.; 2019; 4, pp. 734-747. [DOI: https://dx.doi.org/10.1038/s41564-019-0392-y]

16. Khoury, M.; Cuenca, J.; Cruz, F.F.; Figueroa, F.E.; Rocco, P.R.; Weiss, D.J. Current status of cell-based therapies for respiratory virus infections: Applicability to COVID-19. Eur. Respir. J.; 2020; 55, 2000858. [DOI: https://dx.doi.org/10.1183/13993003.00858-2020]

17. Lansbury, L.; Lim, B.; Baskaran, V.; Lim, W.S. Co-infections in people with COVID-19: A systematic review and meta-analysis. J. Infect.; 2020; 81, pp. 266-275. [DOI: https://dx.doi.org/10.1016/j.jinf.2020.05.046]

18. Mirzaei, R.; Goodarzi, P.; Asadi, M.; Soltani, A.; Aljanabi, H.A.A.; Jeda, A.S.; Karampoor, S. Bacterial co-infections with SARS-CoV-2. IUBMB Life; 2020; 72, pp. 2097-2111. [DOI: https://dx.doi.org/10.1002/iub.2356]

19. McKinney, H.H. Mosaic diseases in the Canary Islands, West Africa, and Gibraltar. J. Agric. Res.; 1929; 39, pp. 557-578.

20. Maliogka, V.I.; Minafra, A.; Saldarelli, P.; Ruiz-García, A.B.; Glasa, M.; Katis, N.; Olmos, A. Recent advances on detection and characterization of fruit tree viruses using high-throughput sequencing technologies. Viruses; 2018; 10, 436. [DOI: https://dx.doi.org/10.3390/v10080436]

21. Skoracka, A.; Rector, B.G.; Hein, G.L. The interface between wheat and the wheat curl mite, Aceria tosichella, the primary vector of globally important viral diseases. Front. Plant Sci.; 2018; 9, 1098. [DOI: https://dx.doi.org/10.3389/fpls.2018.01098]

22. Moreno, A.B.; López-Moya, J.J. When viruses play team sports: Mixed infections in plants. Phytopathology; 2020; 110, pp. 29-48. [DOI: https://dx.doi.org/10.1094/PHYTO-07-19-0250-FI] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31544593]

23. Tatineni, S. Differential Synergistic Interactions among Four Different Wheat-infecting Viruses. Front. Microbiol.; 2021; 12, 800318. [DOI: https://dx.doi.org/10.3389/fmicb.2021.800318] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35095810]

24. Murphy, J.F.; Bowen, K.L. Synergistic disease in pepper caused by the mixed infection of Cucumber mosaic virus and Pepper mottle virus. Phytopathology; 2006; 96, pp. 240-247. [DOI: https://dx.doi.org/10.1094/PHYTO-96-0240] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18944438]

25. Rentería-Canett, I.; Xoconostle-Cázares, B.; Ruiz-Medrano, R.; Rivera-Bustamante, R.F. Geminivirus mixed infection on pepper plants: Synergistic interaction between PHYVV and PepGMV. Virol. J.; 2011; 8, 104. [DOI: https://dx.doi.org/10.1186/1743-422X-8-104]

26. Fraile Pérez, A.; Sacristán Benayas, S.; Garcia-Arenal Rodriguez, F. A quantitative analysis of complementation of deleterious mutants in plant virus populations. Span. J. Agric. Res.; 2008; 6, pp. 195-200. [DOI: https://dx.doi.org/10.5424/sjar/200806S1-388]

27. Latham, J.R.; Wilson, A.K. Transcomplementation and synergism in plants: Implications for viral transgenes?. Mol. Plant Pathol.; 2008; 9, pp. 85-103. [DOI: https://dx.doi.org/10.1111/j.1364-3703.2007.00441.x]

28. Pant, A.; Dsouza, L.; Yang, Z. Alteration in cellular signaling and metabolic reprogramming during viral infection. mBio; 2021; 12, pp. 10-112. [DOI: https://dx.doi.org/10.1128/mBio.00635-21]

29. Hacker, D.L.; Fowler, B.C. Complementation of the host range restriction of southern cowpea mosaic virus in bean by southern bean mosaic virus. Virology; 2000; 266, pp. 140-149. [DOI: https://dx.doi.org/10.1006/viro.1999.0072]

30. Karyeija, R.F.; Kreuze, J.F.; Gibson, R.W.; Valkonen, J.P.T. Synergistic interactions of a potyvirus and a phloem-limited crinivirus in sweet potato plants. Virology; 2000; 269, pp. 26-36. [DOI: https://dx.doi.org/10.1006/viro.1999.0169]

31. Wang, H.; Lyu, R.; Fan, W.; Wang, Y.; Pattanaik, S.; Zhou, X.; Yu, Y.; Liu, Y.; Yang, J.; Li, Y. et al. Cell-type-specific response in host plants to the co-infection by sweet potato viruses. Res. Sq.; 2024; [DOI: https://dx.doi.org/10.1016/j.coviro.2018.12.003]

32. Vanterpool, T.C. Streak or winter blight of tomato in Quebec. Phytopathology; 1926; 16, pp. 311-331.

33. Rowhani, A.; Daubert, S.; Arnold, K.; Al Rwahnih, M.; Klaassen, V.; Golino, D.; Uyemoto, J.K. Synergy between grapevine vitiviruses and grapevine leafroll viruses. Eur. J. Plant Pathol.; 2018; 151, pp. 919-925. [DOI: https://dx.doi.org/10.1007/s10658-018-1426-7]

34. McLeish, M.J.; Fraile, A.; García-Arenal, F. Evolution of plant–virus interactions: Host range and virus emergence. Curr. Opin. Virol.; 2019; 34, pp. 50-55. [DOI: https://dx.doi.org/10.1016/j.coviro.2018.12.003]

35. Anandalakshmi, R.; Pruss, G.J.; Ge, X.; Marathe, R.; Mallory, A.C.; Smith, T.H.; Vance, V.B. A viral suppressor of gene silencing in plants. Proc. Natl. Acad. Sci. USA; 1998; 95, pp. 13079-13084. [DOI: https://dx.doi.org/10.1073/pnas.95.22.13079]

36. Dobbs, E.; Deakin, G.; Bennett, J.; Fleming-Archibald, C.; Jones, I.; Grogan, H.; Burton, K. Viral interactions and pathogenesis during multiple viral infections in Agaricus bisporus. mBio; 2021; 12, e03470-20. [DOI: https://dx.doi.org/10.1128/mBio.03470-20]

37. Tee, E.E.; Faulkner, C. Plasmodesmata and intercellular molecular traffic control. New Phytol.; 2024; 243, pp. 32-47. [DOI: https://dx.doi.org/10.1111/nph.19666]

38. Kumar, G.; Dasgupta, I. Variability, functions and interactions of plant virus movement proteins: What do we know so far?. Microorganisms; 2021; 9, 695. [DOI: https://dx.doi.org/10.3390/microorganisms9040695]

39. Solovyev, A.G.; Atabekova, A.K.; Lezzhov, A.A.; Solovieva, A.D.; Chergintsev, D.A.; Morozov, S.Y. Distinct mechanisms of endomembrane reorganization determine dissimilar transport pathways in plant RNA viruses. Plants; 2022; 11, 2403. [DOI: https://dx.doi.org/10.3390/plants11182403]

40. Morozov, S.Y.; Solovyev, A.G. Mechanisms of plant virus cell-to-cell transport: New lessons from complementation studies. Front. Plant Sci.; 2024; 15, 1453464. [DOI: https://dx.doi.org/10.3389/fpls.2024.1453464]

41. McLeish, M.J.; Fraile, A.; García-Arenal, F. Population genomics of plant viruses: The ecology and evolution of virus emergence. Phytopatholog; 2021; 111, pp. 32-39. [DOI: https://dx.doi.org/10.1094/PHYTO-08-20-0355-FI]

42. Tatineni, S.; Graybosch, R.A.; Hein, G.L.; Wegulo, S.N.; French, R. Wheat cultivar-specific disease synergism and alteration of virus accumulation during co-infection with Wheat streak mosaic virus and Triticum mosaic virus. Phytopathology; 2010; 100, pp. 230-238. [DOI: https://dx.doi.org/10.1094/PHYTO-100-3-0230] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20128696]

43. Friesen, M.L. Social evolution and cheating in plant pathogens. Annu. Rev. Phytopathol.; 2020; 58, pp. 55-75. [DOI: https://dx.doi.org/10.1146/annurev-phyto-010820-012740] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32600178]

44. DaPalma, T.; Doonan, B.P.; Trager, N.M.; Kasman, L.M. A systematic approach to virus–virus interactions. Virus Res.; 2010; 149, pp. 1-9. [DOI: https://dx.doi.org/10.1016/j.virusres.2010.01.002] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20093154]

45. Contreras, M.P.; Pai, H.; Thompson, R.; Marchal, C.; Claeys, J.; Adachi, H.; Kamoun, S. The nucleotide-binding domain of NRC-dependent disease resistance proteins is sufficient to activate downstream helper NLR oligomerization and immune signaling. New Phytol.; 2024; 243, pp. 345-361. [DOI: https://dx.doi.org/10.1111/nph.19818]

46. Shi, X.M.; Miller, H.; Verchot, J.; Carrington, J.C.; Vance, V.B. Mutations in the region encoding the central domain of helper component-proteinase (HC-Pro) eliminate potato virus X/potyviral synergism. Virology; 1997; 231, pp. 35-42. [DOI: https://dx.doi.org/10.1006/viro.1997.8488]

47. Saha, S.; Lõhmus, A.; Dutta, P.; Pollari, M.; Mäkinen, K. Interplay of HCPro and CP in the regulation of Potato Virus A RNA expression and encapsidation. Viruses; 2022; 14, 1233. [DOI: https://dx.doi.org/10.3390/v14061233]

48. Gallo, A.; Valli, A.; Calvo, M.; García, J.A. A functional link between RNA replication and virion assembly in the potyvirus. J. Virol.; 2018; 92, e02179-17. [DOI: https://dx.doi.org/10.1128/JVI.02179-17]

49. Harper, S.J.; Cowell, S.J.; Robertson, C.J.; Dawson, W.O. Differential tropism in roots and shoots infected by Citrus tristeza virus. Virology; 2014; 460, pp. 91-99. [DOI: https://dx.doi.org/10.1016/j.virol.2014.04.035]

50. Mascia, T.; Gallitelli, D. Synergies and antagonisms in virus interactions. Plant Sci.; 2016; 252, pp. 176-192. [DOI: https://dx.doi.org/10.1016/j.plantsci.2016.07.015]

51. Alves-Júnior, M.; Alfenas-Zerbini, P.; Andrade, E.C.; Esposito, D.A.; Silva, F.N.; da Cruz, A.C.F.; Ventrella, M.C.; Otoni, W.C.; Zerbini, F.M. Synergism and negative interference during co-infection of tomato and Nicotiana benthamiana with two bipartite begomoviruses. Virology; 2009; 387, pp. 257-266. [DOI: https://dx.doi.org/10.1016/j.virol.2009.01.046]

52. Wege, C.; Siegmund, D. Synergism of a DNA and an RNA virus: Enhanced tissue infiltration of the begomovirus Abutilon mosaic virus (AbMV) mediated by Cucumber mosaic virus (CMV). Virology; 2007; 357, pp. 10-28. [DOI: https://dx.doi.org/10.1016/j.virol.2006.07.043] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16959287]

53. Savenkov, E.; Valkonen, J. Potyviral Helper—Component Proteinase Expressed in transgenic plants enhances Titers of Potato Leaf Roll Virus but does Not Alleviate Its Phloem limitation. Virology; 2001; 283, pp. 285-293. [DOI: https://dx.doi.org/10.1006/viro.2000.0838] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11336553]

54. Carr, R.J.; Kim, K.S. Evidence that bean golden mosaic virus invades non-phloem tissue in double infections with tobacco mosaic virus. J. Gen. Virol.; 1983; 64, pp. 2489-2492. [DOI: https://dx.doi.org/10.1099/0022-1317-64-11-2489]

55. Li, J.; Wang, J.C.; Ding, T.B.; Chu, D. Synergistic Effects of a Tomato chlorosis virus and Tomato yellow leaf curl virus Mixed Infection on Host Tomato Plants and the Whitefly Vector. Front. Plant Sci.; 2021; 12, 1032. [DOI: https://dx.doi.org/10.3389/fpls.2021.672400]

56. Choi, S.K.; Yoon, J.Y.; Ryu, K.H.; Choi, J.K.; Palukaitis, P.; Park, W.M. Systemic movement of a movement-deficient strain of Cucumber mosaic virus in zucchini squash is facilitated by a cucurbit-infecting potyvirus. J. Gen. Virol.; 2002; 83, pp. 3173-3178. [DOI: https://dx.doi.org/10.1099/0022-1317-83-12-3173]

57. Bennett, C.W. Fenómenos de interferencia entre virus de plantas. Annu. Rev. Microbiol.; 1951; 5, pp. 295-308. [DOI: https://dx.doi.org/10.1146/annurev.mi.05.100151.001455]

58. Bawden, F.C.; Kassanis, B. La supresión de un virus de plantas por otro. Ann. Appl. Biol.; 1945; 32, pp. 52-57. [DOI: https://dx.doi.org/10.1111/j.1744-7348.1945.tb06759.x]

59. Kassanis, B. Interactions of Viruses in Plants. Adv. Virus Res.; 1964; 10, pp. 219-255.

60. Whitaker-Dowling, P.; Youngner, J.S. Viral interference-dominance of mutant viruses over wild-type virus in mixed infections. Microbiol. Rev.; 1987; 51, pp. 179-191. [DOI: https://dx.doi.org/10.1128/mr.51.2.179-191.1987]

61. Sarika, A.M.; Akram, M.; Iquebal, M.A.; Naimuddin, K. Prediction of MHC binding peptides and epitopes from coat protein of mungbean yellow mosaic india virus-Ub05. J. Proteom. Bioinform.; 2010; 3, pp. 173-178.

62. Tenllado, F.; Dıaz-Ruız, J.R. Double-stranded RNA-mediated interference with plant virus infection. J. Virol.; 2001; 75, pp. 12288-12297. [DOI: https://dx.doi.org/10.1128/JVI.75.24.12288-12297.2001] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11711619]

63. Jin, Y.; Zhao, J.; Guo, H. Recent advances in understanding plant antiviral RNAi and viral suppressors of RNAi. Curr. Opin. Virol.; 2021; 46, pp. 65-72. [DOI: https://dx.doi.org/10.1016/j.coviro.2020.12.001]

64. Syller, J. Facilitative and antagonistic interactions between plant viruses in mixed infections. Mol. Plant Pathol.; 2012; 13, pp. 204-216. [DOI: https://dx.doi.org/10.1111/j.1364-3703.2011.00734.x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21726401]

65. Mendez-Lozano, J.; Torres-Pacheco, I.; Fauquet, C.M.; Rivera-Bustamante, R.F. Interactions between geminiviruses in a naturally occurring mixture: Pepper huasteco virus and Pepper golden mosaic virus. Phytopathology; 2003; 93, pp. 270-277. [DOI: https://dx.doi.org/10.1094/PHYTO.2003.93.3.270] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18944336]

66. Saldana, J.; Elena, S.F.; Solé, R.V. Coinfection and superinfection in RNA virus populations: A selection–mutation model. Math. Biosci.; 2003; 183, pp. 135-160. [DOI: https://dx.doi.org/10.1016/S0025-5564(03)00038-5]

67. Ziebell, H.; Carr, J.P. Cross-protection: A century of mystery. Advances in Virus Research; Academic Press: Cambridge, MA, USA, 2010; Volume 76, pp. 211-264.

68. Folimonova, S.Y. Developing an understanding of cross-protection by Citrus tristeza virus. Front. Microbiol.; 2013; 4, 76. [DOI: https://dx.doi.org/10.3389/fmicb.2013.00076]

69. Tatineni, S.; French, R. The coat protein and NIa protease of two Potyviridae family members independently confer superinfection exclusion. J. Virol.; 2016; 90, pp. 10886-10905. [DOI: https://dx.doi.org/10.1128/JVI.01697-16]

70. Zhang, X.; Zhang, S.; Guo, Q.; Sun, R.; Wei, T.; Qu, F. A New Mechanistic Model for Viral Cross Protection and Superinfection Exclusion. Front. Plant Sci.; 2018; 9, 319005. [DOI: https://dx.doi.org/10.3389/fpls.2018.00040]

71. Pechinger, K.; Chooi, K.M.; MacDiarmid, R.M.; Harper, S.J.; Ziebell, H. A new era for mild strain cross-protection. Viruses; 2019; 11, 670. [DOI: https://dx.doi.org/10.3390/v11070670]

72. Kim, K.H.; Lee, Y.T.; Park, S.; Jung, Y.J.; Lee, Y.; Ko, E.J.; Kang, S.M. Neuraminidase expressing virus-like particle vaccine provides effective cross protection against influenza virus. Virology; 2019; 535, pp. 179-188. [DOI: https://dx.doi.org/10.1016/j.virol.2019.07.008]

73. Syller, J. Interspecific and intraspecific interactions among plant viruses in mixed infections. Applied Plant Virology; Academic Press: Cambridge, MA, USA, 2020; pp. 437-453.

74. Jedlinski, H.; Brown, C.M. Cross protection and mutual exclusion by three strains of barley yellow dwarf virus in Avena sativa L. Virology; 1965; 26, pp. 613-621. [DOI: https://dx.doi.org/10.1016/0042-6822(65)90324-7] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/5833319]

75. Dietrich, C.; Maiss, E. Fluorescent labelling reveals spatial separation of potyvirus populations in mixed infected Nicotiana benthamiana plants. J. Gen. Virol.; 2003; 84, pp. 2871-2876. [DOI: https://dx.doi.org/10.1099/vir.0.19245-0] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/13679622]

76. Takeshita, M.; Shigemune, N.; Kikuhara, K.; Furuya, N.; Takanami, Y. Spatial analysis for exclusive interactions between subgroups I and II of Cucumber mosaic virus in cowpea. Virology; 2004; 328, pp. 45-51. [DOI: https://dx.doi.org/10.1016/j.virol.2004.06.046]

77. Takahashi, T.; Sugawara, T.; Yamatsuta, T.; Isogai, M.; Natsuaki, T.; Yoshikawa, N. Analysis of the spatial distribution of identical and two distinct virus populations differently labeled with cyan and yellow fluorescent proteins in coinfected plants. Phytopathology; 2007; 97, pp. 1200-1206. [DOI: https://dx.doi.org/10.1094/PHYTO-97-10-1200]

78. Gallois, J.L.; Moury, B.; German-Retana, S. Role of the genetic background in resistance to plant viruses. Int. J. Mol. Sci.; 2018; 19, 2856. [DOI: https://dx.doi.org/10.3390/ijms19102856]

79. Leeks, A.; Segredo-Otero, E.A.; Sanjuan, R.; West, S.A. Beneficial coinfection can promote within-host viral diversity. Virus Evol.; 2018; 4, vey028. [DOI: https://dx.doi.org/10.1093/ve/vey028]

80. Elena, S.F.; Bedhomme, S.; Carrasco, P.; Cuevas, J.M.; de la Iglesia, F.; Lafforgue, G.; Lalić, J.; Pròsper, À.; Tromas, N.; Zwart, M.P. The evolutionary genetics of emerging plant RNA viruses. Mol. Plant-Microbe Interact.; 2011; 24, pp. 287-293. [DOI: https://dx.doi.org/10.1094/MPMI-09-10-0214]

81. Ren, R.; Zheng, L.; Han, J.; Carvalho, C.P.; Miyashita, S.; Zhang, D.; Qu, F. Intracellular bottlenecking permits no more than three tomato yellow leaf curl virus genomes to initiate replication in a single cell. PLoS Pathog.; 2023; 19, e1011365. [DOI: https://dx.doi.org/10.1371/journal.ppat.1011365]

82. Perdoncini Carvalho, C.; Ren, R.; Han, J.; Qu, F. Natural selection, intracellular bottlenecks of virus populations, and viral superinfection exclusion. Annu. Rev. Virol.; 2022; 9, pp. 121-137. [DOI: https://dx.doi.org/10.1146/annurev-virology-100520-114758]

83. Escobedo-Bonilla, C.M. Mini Review: Virus Interference: History, Types and Occurrence in Crustaceans. Front. Immunol.; 2021; 12, 2332. [DOI: https://dx.doi.org/10.3389/fimmu.2021.674216]

84. Bhattacharyya, D.; Chakraborty, S. Chloroplast: The Trojan horse in plant–virus interaction. Mol. Plant Pathol.; 2018; 19, pp. 504-518. [DOI: https://dx.doi.org/10.1111/mpp.12533] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28056496]

85. Zhao, J.; Zhang, X.; Hong, Y.; Liu, Y. Chloroplast in plant-virus interaction. Front. Microbiol.; 2016; 7, 1565. [DOI: https://dx.doi.org/10.3389/fmicb.2016.01565] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27757106]

86. Bolton, M.D. Primary metabolism and plant defense—Fuel for the fire. Mol. Plant-Microbe Interact.; 2009; 22, pp. 487-497. [DOI: https://dx.doi.org/10.1094/MPMI-22-5-0487]

87. Kale, R.; Hebert, A.E.; Frankel, L.K.; Sallans, L.; Bricker, T.M.; Pospisil, P. Amino acid oxida-tion of the D1 and D2 proteins by oxygen radicals during photoinhibition of Photosystem II. Proc. Natl. Acad. Sci. USA; 2017; 114, pp. 2988-2993. [DOI: https://dx.doi.org/10.1073/pnas.1618922114]

88. Jimbo, H.; Yutthanasirikul, R.; Nagano, T.; Hisabori, T.; Hihara, Y.; Nishiyama, Y. Oxidation of translation factor EF-Tu inhibits the repair of photosystem II. Plant Physiol.; 2018; 176, pp. 2691-2699. [DOI: https://dx.doi.org/10.1104/pp.18.00037]

89. Liu, J.; Yang, J.; Bi, H.; Zhang, P. Why mosaic? Gene expression profiling of African cassava mosaic virus-infected cassava reveals the effect of chlorophyll degradation on symptom development. J. Integr. Plant Biol.; 2014; 56, pp. 122-132. [DOI: https://dx.doi.org/10.1111/jipb.12133]

90. Souza, P.F.; Garcia-Ruiz, H.; Carvalho, F.E. What proteomics can reveal about plant–virus interactions? Photosynthesis-related proteins on the spotlight. Theor. Exp. Plant Physiol.; 2019; 31, pp. 227-248. [DOI: https://dx.doi.org/10.1007/s40626-019-00142-0]

91. Pagán, I.; García-Arenal, F. Tolerance of plants to pathogens: A unifying view. Annu. Rev. Phytopathol.; 2020; 58, pp. 77-96. [DOI: https://dx.doi.org/10.1146/annurev-phyto-010820-012749]

92. Paudel, D.B.; Sanfocon, H. Exploring diversity of mechanisms associated with plant tolerance to virus infection. Front. Plant Sci.; 2018; 9, 1575. [DOI: https://dx.doi.org/10.3389/fpls.2018.01575]

93. Sharma, A.; Sharma, A.; Kumar, R.; Sharma, I.; Vats, A.K. PR proteins: Kyy genes for engeering disease resistance in plants. Crop Improvement; CRC Press: Boca Raton, FL, USA, 2021; pp. 81-98.

94. Prigigallo, M.I.; KrizniK, M.; De Paola, D.; Catalano, D.; Gruden, K.; Finette-Sialer, M.M.; Cillo, F. Ptatovirusy infections alters small RNA metabolism and inmune response in tomato. Viruses; 2019; 11, 1100. [DOI: https://dx.doi.org/10.3390/v11121100]

95. Rimbaud, L.; Dallot, S.; Delaunay, A.; Borron, S.; Soubeyrand, S.; Thébaud, G.; Jacquot, E. Assessing the mismatch between incubation and latent periods for vector-borne diseases: The case of sharka. Phytopathology; 2015; 105, pp. 1408-1416. [DOI: https://dx.doi.org/10.1094/PHYTO-01-15-0014-R] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26512749]

96. Rodrigo, G.; Zwart, M.P.; Elena, S.F. Onset of virus systemic infection in plants is determined by speed of cell-to-cell movement and number of primary infection foci. J. R. Soc. Interface; 2014; 11, 20140555. [DOI: https://dx.doi.org/10.1098/rsif.2014.0555] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24966241]

97. Murant, A.F. Complexes of transmission-dependent and helper viruses. Diagnosis of Plant Virus Diseases; CRC Press: Boca Raton, FL, USA, 2019; pp. 333-358.

98. Hadidi, A.; Sun, L.; Randles, J.W. Modes of viroid transmission. Cells; 2022; 11, 719. [DOI: https://dx.doi.org/10.3390/cells11040719] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/35203368]

99. Owens, R.A. Potato spindle tuber viroid: The simplicity paradox resolved?. Mol. Plant Pathol.; 2007; 8, pp. 549-560. [DOI: https://dx.doi.org/10.1111/j.1364-3703.2007.00418.x]

100. Malmstrom, C.M.; Bigelow, P.; Trębicki, P.; Busch, A.K.; Friel, C.; Cole, E.; Abdel-Azim, H.; Phillippo, C.; Alexander, H.M. Crop-associated virus reduces the rooting depth of non-crop perennial native grass more than non-crop-associated virus with known viral suppressor of RNA silencing (VSR). Virus Res.; 2017; 241, pp. 172-184. [DOI: https://dx.doi.org/10.1016/j.virusres.2017.07.006]

101. Liu, Y.; Sun, B.; Wang, X.; Zheng, C.; Zhou, G. Three digoxigenin-labeled cDNA probes for specific detection of the natural population of Barley yellow dwarf viruses in China by dot-blot hybridization. J. Virol. Methods; 2007; 145, pp. 22-29. [DOI: https://dx.doi.org/10.1016/j.jviromet.2007.05.006]

102. Medina-Salguero, A.X.; Cornejo-Franco, J.F.; Grinstead, S.; Mowery, J.; Mollov, D.; Quito-Avila, D.F. Genetic characterization of a mild isolate of papaya ringspot virus type-P (PRSV-P) and assessment of its cross-protection potential under greenhouse and field conditions. PLoS ONE; 2021; 16, e0241652. [DOI: https://dx.doi.org/10.1371/journal.pone.0241652]

103. Huang, X.D.; Fang, L.; Gu, Q.S.; Tian, Y.P.; Geng, C.; Li, X.D. Cross protection against the watermelon strain of Papaya ringspot virus through modification of viral RNA silencing suppressor. Virus Res.; 2019; 265, pp. 166-171. [DOI: https://dx.doi.org/10.1016/j.virusres.2019.03.016]

104. Folimonova, S.Y.; Achor, D.; Bar-Joseph, M. Walking together: Cross-protection, genome conservation, and the replication machinery of Citrus tristeza virus. Viruses; 2020; 12, 1353. [DOI: https://dx.doi.org/10.3390/v12121353]

105. Ranjan, P.; Bhatt, B.; Singh, A.K. Implications of Mixed Infection on Disease Pathogenicity and Epidemiology. New and Emerging Plant Viruses; Apple Academic Press: Palm Bay, FL, USA, 2025; pp. 275-296.

106. Ghosh, S.K.; Chatterjee, T. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Associated Proteins (Cas)[CRISPR–Cas]: An Emerging Technique in Plant Disease Detection and Management. Gene Editing in Plants: CRISPR-Cas and Its Applications; Springer Nature: Singapore, 2024; pp. 589-645.

107. Hwarari, D.; Radani, Y.; Ke, Y.; Chen, J.; Yang, L. CRISPR/Cas genome editing in plants: Mechanisms, applications, and overcoming bottlenecks. Funct. Integr. Genom.; 2024; 24, 50. [DOI: https://dx.doi.org/10.1007/s10142-024-01314-1]

108. Mahas, A.; Aman, R.; Mahfouz, M. CRISPR-Cas13d mediates robust RNA virus interference in plants. Genome Biol.; 2019; 20, 263. [DOI: https://dx.doi.org/10.1186/s13059-019-1881-2] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31791381]

109. Robertson, G. Establishing the CRISPR/Cas13a Genome Editing System in Nicotiana Benthamiana for RNA Targeting Applications. Ph.D. Thesis; Stellenbosch University: Stellenbosch, South Africa, 2021.

110. Bocos-Asenjo, I.T.; Niño-Sánchez, J.; Ginésy, M.; Diez, J.J. New insights on the integrated management of plant diseases by RNA strategies: Mycoviruses and RNA interference. Int. J. Mol. Sci.; 2022; 23, 9236. [DOI: https://dx.doi.org/10.3390/ijms23169236] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/36012499]

111. Sanchez-Vargas, I.; Travanty, E.A.; Keene, K.M.; Franz, A.W.; Beaty, B.J.; Blair, C.D.; Olson, K.E. RNA interference, arthropod-borne viruses, and mosquitoes. Virus Res.; 2004; 102, pp. 65-74. [DOI: https://dx.doi.org/10.1016/j.virusres.2004.01.017] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15068882]

112. Choua, M.; Bonachela, J.A. Ecological and evolutionary consequences of viral plasticity. Am. Nat.; 2019; 193, pp. 346-358. [DOI: https://dx.doi.org/10.1086/701668] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30794445]

113. Marshall, J.M.; Raban, R.R.; Kandul, N.P.; Edula, J.R.; León, T.M.; Akbari, O.S. Winning the tug-of-war between effector gene design and pathogen evolution in vector population replacement strategies. Front. Genet.; 2019; 10, 1072. [DOI: https://dx.doi.org/10.3389/fgene.2019.01072]

114. Islam, K.; Kumar, N.; Yadava, S.K.; Momo, J.; Ramchiary, N. Genomic Designing for breeding biotic stress resistant Pepper Crop. Genomic Designing for Biotic Stress Resistant Vegetable Crops; Springer International Publishing: Cham, Switzerland, 2022; pp. 65-145.

115. Di Carli, M.; Benvenuto, E.; Donini, M. Recent insights into plant–virus interactions through proteomic analysis. J. Proteome Res.; 2012; 11, pp. 4765-4780. [DOI: https://dx.doi.org/10.1021/pr300494e]

116. Hernández, J.A.; Gullner, G.; Clemente-Moreno, M.J.; Künstler, A.; Juhász, C.; Díaz-Vivancos, P.; Király, L. Oxidative stress and antioxidative responses in plant–virus interactions. Physiol. Mol. Plant Pathol.; 2016; 94, pp. 134-148. [DOI: https://dx.doi.org/10.1016/j.pmpp.2015.09.001]

117. García-Marcos, A.; Pacheco, R.; Martiáñez, J.; González-Jara, P.; Díaz-Ruíz, J.R.; Tenllado, F. Transcriptional changes and oxidative stress associated with the synergistic interaction between Potato virus X and Potato virus Y and their relationship with symptom expression. Mol. Plant-Microbe Interact.; 2009; 22, pp. 1431-1444. [DOI: https://dx.doi.org/10.1094/MPMI-22-11-1431]

118. Ding, S.W. Transgene silencing, RNA interference, and the antiviral defense mechanism directed by small interfering RNAs. Phytopathology; 2023; 113, pp. 616-625. [DOI: https://dx.doi.org/10.1094/PHYTO-10-22-0358-IA]

119. Zulfiqar, S.; Farooq, M.A.; Zhao, T.; Wang, P.; Tabusam, J.; Wang, Y.; Xuan, S.; Zhao, J.; Chen, X.; Shen, S. et al. Virus-Induced Gene Silencing (VIGS): A Powerful Tool for Crop Improvement and Its Advancement towards Epigenetics. Int. J. Mol. Sci.; 2023; 24, 5608. [DOI: https://dx.doi.org/10.3390/ijms24065608]

120. Paudel, S. Effects of Plant Viruses on Vectors and Non-Vector Herbivores in Three Different Pathosystems. Ph.D. Thesis; Louisiana State University and Agricultural Mechanical College: Baton Rouge, LA, USA, 2019.

121. Shams-Bakhsh, M.; Canto, T.; Palukaitis, P. Enhanced resistance and neutralization of defense responses by suppressors of RNA silencing. Virus Res.; 2007; 130, pp. 103-109. [DOI: https://dx.doi.org/10.1016/j.virusres.2007.05.023] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17617488]

122. Xu, P.; Chen, F.; Mannas, J.P.; Feldman, T.; Sumner, L.W.; Roossinck, M.J. Virus infection improves drought tolerance. New Phytol.; 2008; 180, pp. 911-921. [DOI: https://dx.doi.org/10.1111/j.1469-8137.2008.02627.x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18823313]

123. Bourdin, D.; Lecoq, H. Evidence that heteroencapsidation between two potyviruses is involved in aphid transmission of a non-aphid-transmissible isolate from mixed infections. Phytopathology; 1991; 81, pp. 1459-1464. [DOI: https://dx.doi.org/10.1094/Phyto-81-1459]

124. James, D.; Varga, A.; Pallas, V.; Candresse, T. Trategies for simultaneous detection of multiple plant viruses. Can. J. Plant Pathol.; 2006; 28, pp. 16-29. [DOI: https://dx.doi.org/10.1080/07060660609507267]

125. Bacci, L.; Convertini, S.; Rossaro, B. A review of sulfoxaflor, a derivative of biological acting substances as a class of insecticides with a broad range of action against many insect pests. J. Entomol. Acarol. Res.; 2018; 50, [DOI: https://dx.doi.org/10.4081/jear.2018.7836]

126. Sarwar, M.; Shad, N.A.; Batool, R. Integrated management of vectored viral diseases of plants. Applied Plant Virology; Academic Press: Cambridge, MA, USA, 2020; pp. 707-724.

127. Warghane, A.; Saini, R.; Shri, M.; Andankar, I.; Ghosh, D.K.; Chopade, B.A. Application of nanoparticles for management of plant viral pathogen: Current status and future prospects. Virology; 2024; 592, 109998. [DOI: https://dx.doi.org/10.1016/j.virol.2024.109998]

128. Vargas-Hernandez, M.; Macias-Bobadilla, I.; Guevara-Gonzalez, R.G.; Rico-Garcia, E.; Ocampo-Velazquez, R.V.; Avila-Juarez, L.; Torres-Pacheco, I. Nanoparticles as potential antivirals in agriculture. Agriculture; 2020; 10, 444. [DOI: https://dx.doi.org/10.3390/agriculture10100444]

129. Mejía-Teniente, L.; Durán-Flores, B.A.; Torres-Pacheco, I.; González-Chavira, M.M.; Rivera-Bustamante, R.F.; Feregrino-Perez, A.A.; Pérez-Ramírez, I.; Rocha-Guzmán, N.E.; Reynoso-Camacho, R.; Guevara-González, R.G. Hydrogen peroxide protects pepper (Capsicum annuum L.) against pepper golden mosaic geminivirus (PepGMV) infections. Physiol. Mol. Plant Pathol.; 2019; 106, pp. 23-29. [DOI: https://dx.doi.org/10.1016/j.pmpp.2018.11.008]

130. Shahriar, S.A.; Islam, M.N.; Chun, C.N.W.; Rahim, M.A.; Paul, N.C.; Uddain, J.; Siddiquee, S. Control of plant viral diseases by CRISPR/Cas9: Resistance mechanisms, strategies and challenges in food crops. Plants; 2021; 10, 1264. [DOI: https://dx.doi.org/10.3390/plants10071264]

131. Khatodia, S.; Bhatotia, K.; Tuteja, N. Development of CRISPR/Cas9 mediated virus resistance in agriculturally important crops. Bioengineered; 2017; 8, pp. 274-279. [DOI: https://dx.doi.org/10.1080/21655979.2017.1297347]