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Key Words mutants, antigenicity, reassortment, recombination, pathogenicity
* Abstract Influenza A viruses contain genomes composed of eight separate segments of negative-sense RNA. Circulating human strains are notorious for their tendency to accumulate mutations from one year to the next and cause recurrent epidemics. However, the segmented nature of the genome also allows for the exchange of entire genes between different viral strains. The ability to manipulate influenza gene segments in various combinations in the laboratory has contributed to its being one of the best characterized viruses, and studies on influenza have provided key contributions toward the understanding of various aspects of virology in general. However, the genetic plasticity of influenza viruses also has serious potential implications regarding vaccine design, pathogenicity, and the capacity for novel viruses to emerge from natural reservoirs and cause global pandemics.
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INTRODUCTION
Influenza A viruses are lipid-enveloped viruses containing a genome composed of eight strands of negative-sense RNA that encode ten viral proteins. These gene segments are encapsidated in a virally encoded nucleoprotein (NP), and the ribonucleoprotein (RNP) structures are associated with the three subunits of the viral polymerase (PB1, PB2, and PA). Virus particle formation occurs at the surface membrane of infected cells, where budding occurs from regions of the membrane at which the viral glycoproteins, hemagglutinin (HA) and neuraminidase (NA), have accumulated. The viral matrix protein (M1) is the most abundant component of the virion and is thought to play a pivotal role in the process of assembly and budding. Details on the mechanism of assembly are still forthcoming, but it is often assumed that M1 interacts with the RNPs and the cytoplasmic domains of HA, NA, and possibly the third integral membrane protein M2. The two other viral proteins, NS1 and NS2, were initially designated as nonstructural proteins, but there is now evidence for the presence of NS2 in virions.
Depending on the virus strain and passage history, influenza A virions can exhibit a variety of shapes and sizes, ranging from fairly spherical particles of approximately 100 nm in diameter to elongated filamentous forms of the virus (69,71). Initial human isolates tend to be largely of the filamentous type (26), but upon continuous propagation in the laboratory, viruses with more spherical morphology can be selected...