Experiments Investigating the Competitive Growth Advantage of Two Different Genotypes of Human Metapneumovirus: Implications for the Alternation of Genotype Prevalence

Abstract

Human metapneumovirus (hMPV) is an important pathogen that causes upper and lower respiratory tract infections in children worldwide. hMPV has two major genotypes, hMPV-A and hMPV-B. Epidemiological studies have shown that the two hMPV genotypes alternate in predominance worldwide in recent years. Co-circulation of the two genotypes of hMPV was usually observed and there is no study about the interaction between them, such as competitive replication, which maybe the possible mechanisms for alternating prevalence of subtypes. Our present study have used two different genotypes of hMPV (genotype A: NL/1/00; B: NL/1/99) in different proportions in animal model (BALB/c mice) and cell model (Vero-E6) separately. The result showed that the competitive growth does exist in BALB/c mice, genotype B had a strong competitive advantage. However, genotype B did not cause more severe disease than non-predominant (genotype A) or mixed strains in the study, which were evaluated by the body weight, airway hyperresponsiveness and lung pathology of mouse. In cell model, competitive growth and the two genotypes alternately prevalence were observed. In summary, we confirmed that there was a competitive replication between hMPV genotype A and B, and no difference in disease severity caused by the two subtypes. This study shows a new insight to understand the alternation of hMPV genotype prevalence through genotype competition and provide experimental evidence for disease control and vaccine design.