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Seasonal H3N2 and 2009 pandemic H1N1 influenza A viruses reassort efficiently but produce attenuated progeny

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  • Seasonal H3N2 and 2009 pandemic H1N1 influenza A viruses reassort efficiently but produce attenuated progeny

    J Virol. 2017 Jun 21. pii: JVI.00830-17. doi: 10.1128/JVI.00830-17. [Epub ahead of print]
    Seasonal H3N2 and 2009 pandemic H1N1 influenza A viruses reassort efficiently but produce attenuated progeny.

    Phipps KL1, Marshall N1, Tao H1, Danzy S1, Onuoha N1, Steel J1, Lowen AC2.
    Author information

    Abstract

    Reassortment of gene segments between co-infecting influenza A viruses (IAV) facilitates viral diversification and has significant epidemiological impact on seasonal and pandemic influenza. Since 1977, human IAVs of H1N1 and H3N2 subtypes have co-circulated with relatively few documented cases of reassortment. We evaluated the potential for viruses of the 2009 pandemic H1N1 (pH1N1) and seasonal H3N2 lineages to reassort under experimental conditions. Results of heterologous co-infections with pH1N1 and H3N2 viruses were compared to those obtained following co-infection with homologous, genetically tagged, pH1N1 viruses as a control. High genotype diversity was observed among progeny of both co-infections; however, diversity was more limited following heterologous co-infection. Pairwise analysis of genotype patterns revealed that homologous reassortment was random while heterologous reassortment was characterized by specific biases. pH1N1/H3N2 reassortant genotypes produced under single cycle co-infection conditions showed a strong preference for homologous PB2-PA combinations and general preferences for the H3N2 NA, pH1N1 M, and the H3N2 PB2 except when paired with the pH1N1 PA or NP. Multicycle co-infection results corroborated these findings and revealed an additional preference for the H3N2 HA. Segment compatibility was further investigated by measuring chimeric polymerase activity and growth of selected reassortants in human tracheobronchial epithelial cells. In guinea pigs inoculated with a mixture of viruses, parental H3N2 viruses dominated but reassortants also infected and transmitted to cage mates. Taken together, our results indicate that strong intrinsic barriers to reassortment between seasonal H3N2 and pH1N1 viruses are few, but that the reassortants formed are attenuated relative to parental strains.IMPORTANCE The genome of IAV is relatively simple, comprising eight RNA segments, each of which typically encodes one or two proteins. Each viral protein carries out multiple functions in coordination with other viral components and the machinery of the cell. When two IAV co-infect a cell, they can exchange genes through reassortment. The resultant progeny viruses often suffer fitness defects due to sub-optimal interactions among divergent viral components. The genetic diversity generated through reassortment can facilitate the emergence of novel outbreak strains. Thus, it is important to understand the efficiency of reassortment and the factors that limit its potential. The research described here offers new tools for studying reassortment between two strains of interest, and applies those tools to viruses of the 2009 pandemic H1N1 and seasonal H3N2 lineages, which currently co-circulate in humans and therefore have the potential to give rise to novel epidemic strains.
    Copyright ? 2017 American Society for Microbiology.


    PMID: 28637755 DOI: 10.1128/JVI.00830-17
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