The genesis and spread of reassortment human influenza A/H3N2 viruses conferring adamantane resistance

Lone Simonsen, Cecile Viboud, Bryan T. Grenfell, Jonathan Dushoff, Lance Jennings, Marita Smit, Catherine Macken, Mami Hata, Julia Gog, Mark Miller, Edward C. Holmes

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Resumé

A dramatic rise in the frequency of resistance to adamantane drugs by influenza A (H3N2) viruses has occurred in recent years -- from approximately 2% to approximately 90% in multiple countries worldwide-and associated with a single S31N amino acid replacement in the viral matrix M2 protein. To explore the emergence and spread of these adamantane resistant viruses we performed a phylogenetic analysis of recently sampled complete A/H3N2 genome sequences. Strikingly, all adamantane resistant viruses belonged to a single lineage (the "N-lineage") characterized by 17 amino acid replacements across the viral genome. Further, our analysis revealed that the genesis of the N-lineage was due to a 4+4 segment reassortment event involving 2 distinct lineages of influenza A/H3N2 virus. A subsequent study of hemagglutinin HA1 sequences suggested that the N-lineage was circulating widely in Asia during 2005, and then dominated the Northern hemisphere 2005-2006 season in Japan and the USA. Given the infrequent use of adamantane drugs in many countries, as well as the decades of use in the US associated with little drug resistance, we propose that the globally increasing frequency of adamantane resistance is more likely attributable to its interaction with fitness-enhancing mutations at other genomic sites rather than to direct drug selection pressure. This implies that adamantanes may not be useful for treatment and prophylaxis against influenza viruses in the long term. More generally, these findings illustrate that drug selection pressure is not the sole factor determining the evolution and maintenance of drug resistance in human pathogens.
OriginalsprogEngelsk
TidsskriftMolecular Biology and Evolution
Vol/bind24
Udgave nummer8
Sider (fra-til)1811-1820
ISSN0737-4038
StatusUdgivet - 2007

Emneord

    Citer dette

    Simonsen, L., Viboud, C., Grenfell, B. T., Dushoff, J., Jennings, L., Smit, M., ... Holmes, E. C. (2007). The genesis and spread of reassortment human influenza A/H3N2 viruses conferring adamantane resistance. Molecular Biology and Evolution, 24(8), 1811-1820.
    Simonsen, Lone ; Viboud, Cecile ; Grenfell, Bryan T. ; Dushoff, Jonathan ; Jennings, Lance ; Smit, Marita ; Macken, Catherine ; Hata, Mami ; Gog, Julia ; Miller, Mark ; Holmes, Edward C. / The genesis and spread of reassortment human influenza A/H3N2 viruses conferring adamantane resistance. I: Molecular Biology and Evolution. 2007 ; Bind 24, Nr. 8. s. 1811-1820.
    @article{9c9237c6d4a44cacb563f91187fae5df,
    title = "The genesis and spread of reassortment human influenza A/H3N2 viruses conferring adamantane resistance",
    abstract = "A dramatic rise in the frequency of resistance to adamantane drugs by influenza A (H3N2) viruses has occurred in recent years -- from approximately 2{\%} to approximately 90{\%} in multiple countries worldwide-and associated with a single S31N amino acid replacement in the viral matrix M2 protein. To explore the emergence and spread of these adamantane resistant viruses we performed a phylogenetic analysis of recently sampled complete A/H3N2 genome sequences. Strikingly, all adamantane resistant viruses belonged to a single lineage (the {"}N-lineage{"}) characterized by 17 amino acid replacements across the viral genome. Further, our analysis revealed that the genesis of the N-lineage was due to a 4+4 segment reassortment event involving 2 distinct lineages of influenza A/H3N2 virus. A subsequent study of hemagglutinin HA1 sequences suggested that the N-lineage was circulating widely in Asia during 2005, and then dominated the Northern hemisphere 2005-2006 season in Japan and the USA. Given the infrequent use of adamantane drugs in many countries, as well as the decades of use in the US associated with little drug resistance, we propose that the globally increasing frequency of adamantane resistance is more likely attributable to its interaction with fitness-enhancing mutations at other genomic sites rather than to direct drug selection pressure. This implies that adamantanes may not be useful for treatment and prophylaxis against influenza viruses in the long term. More generally, these findings illustrate that drug selection pressure is not the sole factor determining the evolution and maintenance of drug resistance in human pathogens.",
    keywords = "influenza virus, Adamantane resistance, Reassortment, hitch-hiking, natural selection",
    author = "Lone Simonsen and Cecile Viboud and Grenfell, {Bryan T.} and Jonathan Dushoff and Lance Jennings and Marita Smit and Catherine Macken and Mami Hata and Julia Gog and Mark Miller and Holmes, {Edward C.}",
    year = "2007",
    language = "English",
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    journal = "Molecular Biology and Evolution",
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    Simonsen, L, Viboud, C, Grenfell, BT, Dushoff, J, Jennings, L, Smit, M, Macken, C, Hata, M, Gog, J, Miller, M & Holmes, EC 2007, 'The genesis and spread of reassortment human influenza A/H3N2 viruses conferring adamantane resistance' Molecular Biology and Evolution, bind 24, nr. 8, s. 1811-1820.

    The genesis and spread of reassortment human influenza A/H3N2 viruses conferring adamantane resistance. / Simonsen, Lone; Viboud, Cecile; Grenfell, Bryan T.; Dushoff, Jonathan; Jennings, Lance; Smit, Marita; Macken, Catherine; Hata, Mami; Gog, Julia; Miller, Mark; Holmes, Edward C.

    I: Molecular Biology and Evolution, Bind 24, Nr. 8, 2007, s. 1811-1820.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - The genesis and spread of reassortment human influenza A/H3N2 viruses conferring adamantane resistance

    AU - Simonsen, Lone

    AU - Viboud, Cecile

    AU - Grenfell, Bryan T.

    AU - Dushoff, Jonathan

    AU - Jennings, Lance

    AU - Smit, Marita

    AU - Macken, Catherine

    AU - Hata, Mami

    AU - Gog, Julia

    AU - Miller, Mark

    AU - Holmes, Edward C.

    PY - 2007

    Y1 - 2007

    N2 - A dramatic rise in the frequency of resistance to adamantane drugs by influenza A (H3N2) viruses has occurred in recent years -- from approximately 2% to approximately 90% in multiple countries worldwide-and associated with a single S31N amino acid replacement in the viral matrix M2 protein. To explore the emergence and spread of these adamantane resistant viruses we performed a phylogenetic analysis of recently sampled complete A/H3N2 genome sequences. Strikingly, all adamantane resistant viruses belonged to a single lineage (the "N-lineage") characterized by 17 amino acid replacements across the viral genome. Further, our analysis revealed that the genesis of the N-lineage was due to a 4+4 segment reassortment event involving 2 distinct lineages of influenza A/H3N2 virus. A subsequent study of hemagglutinin HA1 sequences suggested that the N-lineage was circulating widely in Asia during 2005, and then dominated the Northern hemisphere 2005-2006 season in Japan and the USA. Given the infrequent use of adamantane drugs in many countries, as well as the decades of use in the US associated with little drug resistance, we propose that the globally increasing frequency of adamantane resistance is more likely attributable to its interaction with fitness-enhancing mutations at other genomic sites rather than to direct drug selection pressure. This implies that adamantanes may not be useful for treatment and prophylaxis against influenza viruses in the long term. More generally, these findings illustrate that drug selection pressure is not the sole factor determining the evolution and maintenance of drug resistance in human pathogens.

    AB - A dramatic rise in the frequency of resistance to adamantane drugs by influenza A (H3N2) viruses has occurred in recent years -- from approximately 2% to approximately 90% in multiple countries worldwide-and associated with a single S31N amino acid replacement in the viral matrix M2 protein. To explore the emergence and spread of these adamantane resistant viruses we performed a phylogenetic analysis of recently sampled complete A/H3N2 genome sequences. Strikingly, all adamantane resistant viruses belonged to a single lineage (the "N-lineage") characterized by 17 amino acid replacements across the viral genome. Further, our analysis revealed that the genesis of the N-lineage was due to a 4+4 segment reassortment event involving 2 distinct lineages of influenza A/H3N2 virus. A subsequent study of hemagglutinin HA1 sequences suggested that the N-lineage was circulating widely in Asia during 2005, and then dominated the Northern hemisphere 2005-2006 season in Japan and the USA. Given the infrequent use of adamantane drugs in many countries, as well as the decades of use in the US associated with little drug resistance, we propose that the globally increasing frequency of adamantane resistance is more likely attributable to its interaction with fitness-enhancing mutations at other genomic sites rather than to direct drug selection pressure. This implies that adamantanes may not be useful for treatment and prophylaxis against influenza viruses in the long term. More generally, these findings illustrate that drug selection pressure is not the sole factor determining the evolution and maintenance of drug resistance in human pathogens.

    KW - influenza virus

    KW - Adamantane resistance

    KW - Reassortment

    KW - hitch-hiking

    KW - natural selection

    M3 - Journal article

    VL - 24

    SP - 1811

    EP - 1820

    JO - Molecular Biology and Evolution

    JF - Molecular Biology and Evolution

    SN - 0737-4038

    IS - 8

    ER -