http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1001022
Susu Duan<sup>1</sup><sup>,</sup><sup>2</sup>, David A. Boltz<sup>1</sup><sup>?</sup>, Patrick Seiler<sup>1</sup>, Jiang Li<sup>3</sup>, Karoline Bragstad<sup>4</sup>, Lars P. Nielsen<sup>4</sup>, Richard J. Webby<sup>1</sup>, Robert G. Webster<sup>1</sup><sup>,</sup><sup>2</sup>, Elena A. Govorkova<sup>1</sup><sup>*</sup>
1 Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America, 2 Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America, 3 Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America, 4 National Influenza Laboratory, Department of Virology, Statens Serum Institute, Copenhagen, Denmark
The increasing concern about oseltamivir-resistant H1N1/2009 viruses prompted us to evaluate transmissibility and growth fitness of one oseltamivir-resistant variant. The infectivity and transmissibility (and thus the clinical relevance) of several NA inhibitor-resistant influenza viruses have previously been studied in experimental animal models [26]?[29]. These studies differed in the influenza A subtypes studied (H1N1, H3N2, or H5N1), the NA mutations involved (H275Y, R292K, E119V or I222V), the animal model used (ferret or guinea pig), and the transmission routes studied (direct contact and respiratory droplets); in these studies, the transmissibility of most of the NA inhibitor-resistant influenza viruses was to some extent less efficient. Here we characterized in vitro and in a ferret model a pair of pandemic H1N1/2009 clinical isolates. The pandemic A/Denmark/524/09 (A/DM/524/09) and A/Denmark/528/09 (A/DM/528/09) viruses were isolated from a small cluster of patients with H1N1/2009 virus infection [30]. The A/DM/528/09 virus, carrying the H275Y NA mutation, was isolated from a patient on oseltamivir prophylaxis, and its ancestor is likely to have been A/DM/524/09 virus. By recapitulating two natural routes of influenza virus transmission in ferrets, we found that the oseltamivir-resistant virus was less transmissible than its sensitive counterpart through the respiratory droplet route but retained efficient transmission through direct contact.
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Susu Duan<sup>1</sup><sup>,</sup><sup>2</sup>, David A. Boltz<sup>1</sup><sup>?</sup>, Patrick Seiler<sup>1</sup>, Jiang Li<sup>3</sup>, Karoline Bragstad<sup>4</sup>, Lars P. Nielsen<sup>4</sup>, Richard J. Webby<sup>1</sup>, Robert G. Webster<sup>1</sup><sup>,</sup><sup>2</sup>, Elena A. Govorkova<sup>1</sup><sup>*</sup>
1 Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America, 2 Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America, 3 Hartwell Center for Bioinformatics and Biotechnology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America, 4 National Influenza Laboratory, Department of Virology, Statens Serum Institute, Copenhagen, Denmark
The increasing concern about oseltamivir-resistant H1N1/2009 viruses prompted us to evaluate transmissibility and growth fitness of one oseltamivir-resistant variant. The infectivity and transmissibility (and thus the clinical relevance) of several NA inhibitor-resistant influenza viruses have previously been studied in experimental animal models [26]?[29]. These studies differed in the influenza A subtypes studied (H1N1, H3N2, or H5N1), the NA mutations involved (H275Y, R292K, E119V or I222V), the animal model used (ferret or guinea pig), and the transmission routes studied (direct contact and respiratory droplets); in these studies, the transmissibility of most of the NA inhibitor-resistant influenza viruses was to some extent less efficient. Here we characterized in vitro and in a ferret model a pair of pandemic H1N1/2009 clinical isolates. The pandemic A/Denmark/524/09 (A/DM/524/09) and A/Denmark/528/09 (A/DM/528/09) viruses were isolated from a small cluster of patients with H1N1/2009 virus infection [30]. The A/DM/528/09 virus, carrying the H275Y NA mutation, was isolated from a patient on oseltamivir prophylaxis, and its ancestor is likely to have been A/DM/524/09 virus. By recapitulating two natural routes of influenza virus transmission in ferrets, we found that the oseltamivir-resistant virus was less transmissible than its sensitive counterpart through the respiratory droplet route but retained efficient transmission through direct contact.