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Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model.

Abstract

Avian influenza A H5N1 viruses continue to spread globally among birds, resulting in occasional transmission of virus from infected poultry to humans. Probable human-to-human transmission has been documented rarely, but H5N1 viruses have not yet acquired the ability to transmit efficiently among humans, an essential property of a pandemic virus. The pandemics of 1957 and 1968 were caused by avian-human reassortant influenza viruses that had acquired human virus-like receptor binding properties. However, the relative contribution of human internal protein genes or other molecular changes to the efficient transmission of influenza viruses among humans remains poorly understood. Here, we report on a comparative ferret model that parallels the efficient transmission of H3N2 human viruses and the poor transmission of H5N1 avian viruses in humans. In this model, an H3N2 reassortant virus with avian virus internal protein genes exhibited efficient replication but inefficient transmission, whereas H5N1 reassortant viruses with four or six human virus internal protein genes exhibited reduced replication and no transmission. These findings indicate that the human virus H3N2 surface protein genes alone did not confer efficient transmissibility and that acquisition of human virus internal protein genes alone was insufficient for this 1997 H5N1 virus to develop pandemic capabilities, even after serial passages in a mammalian host. These results highlight the complexity of the genetic basis of influenza virus transmissibility and suggest that H5N1 viruses may require further adaptation to acquire this essential pandemic trait.

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  • Authors+Show Affiliations

    ,

    Influenza Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.

    , , , , , , , , , , , , , ,

    Source

    MeSH

    Animals
    Disease Models, Animal
    Disease Outbreaks
    Ferrets
    Humans
    Influenza A Virus, H3N2 Subtype
    Influenza A Virus, H5N1 Subtype
    Influenza, Human
    Male
    Models, Biological
    Reassortant Viruses
    Virus Replication

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    16880383

    Citation

    Maines, Taronna R., et al. "Lack of Transmission of H5N1 Avian-human Reassortant Influenza Viruses in a Ferret Model." Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 32, 2006, pp. 12121-6.
    Maines TR, Chen LM, Matsuoka Y, et al. Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model. Proc Natl Acad Sci USA. 2006;103(32):12121-6.
    Maines, T. R., Chen, L. M., Matsuoka, Y., Chen, H., Rowe, T., Ortin, J., ... Katz, J. M. (2006). Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model. Proceedings of the National Academy of Sciences of the United States of America, 103(32), pp. 12121-6.
    Maines TR, et al. Lack of Transmission of H5N1 Avian-human Reassortant Influenza Viruses in a Ferret Model. Proc Natl Acad Sci USA. 2006 Aug 8;103(32):12121-6. PubMed PMID: 16880383.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model. AU - Maines,Taronna R, AU - Chen,Li-Mei, AU - Matsuoka,Yumiko, AU - Chen,Hualan, AU - Rowe,Thomas, AU - Ortin,Juan, AU - Falcón,Ana, AU - Nguyen,Tran Hien, AU - Mai,Le Quynh, AU - Sedyaningsih,Endang R, AU - Harun,Syahrial, AU - Tumpey,Terrence M, AU - Donis,Ruben O, AU - Cox,Nancy J, AU - Subbarao,Kanta, AU - Katz,Jacqueline M, Y1 - 2006/07/31/ PY - 2006/8/2/pubmed PY - 2006/9/29/medline PY - 2006/8/2/entrez SP - 12121 EP - 6 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 103 IS - 32 N2 - Avian influenza A H5N1 viruses continue to spread globally among birds, resulting in occasional transmission of virus from infected poultry to humans. Probable human-to-human transmission has been documented rarely, but H5N1 viruses have not yet acquired the ability to transmit efficiently among humans, an essential property of a pandemic virus. The pandemics of 1957 and 1968 were caused by avian-human reassortant influenza viruses that had acquired human virus-like receptor binding properties. However, the relative contribution of human internal protein genes or other molecular changes to the efficient transmission of influenza viruses among humans remains poorly understood. Here, we report on a comparative ferret model that parallels the efficient transmission of H3N2 human viruses and the poor transmission of H5N1 avian viruses in humans. In this model, an H3N2 reassortant virus with avian virus internal protein genes exhibited efficient replication but inefficient transmission, whereas H5N1 reassortant viruses with four or six human virus internal protein genes exhibited reduced replication and no transmission. These findings indicate that the human virus H3N2 surface protein genes alone did not confer efficient transmissibility and that acquisition of human virus internal protein genes alone was insufficient for this 1997 H5N1 virus to develop pandemic capabilities, even after serial passages in a mammalian host. These results highlight the complexity of the genetic basis of influenza virus transmissibility and suggest that H5N1 viruses may require further adaptation to acquire this essential pandemic trait. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/16880383/Lack_of_transmission_of_H5N1_avian_human_reassortant_influenza_viruses_in_a_ferret_model_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=16880383 DB - PRIME DP - Unbound Medicine ER -