Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses
- 10 September 2012
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 109 (39), 15900-15905
- https://doi.org/10.1073/pnas.1205576109
Abstract
Efficient worldwide swine surveillance for influenza A viruses is urgently needed; the emergence of a novel reassortant pandemic H1N1 (pH1N1) virus in 2009 demonstrated that swine can be the direct source of pandemic influenza and that the pandemic potential of viruses prevalent in swine populations must be monitored. We used the ferret model to assess the pathogenicity and transmissibility of predominant Korean triple-reassortant swine (TRSw) H1N2 and H3N2 influenza viruses genetically related to North American strains. Although most of the TRSw viruses were moderately pathogenic, one [A/Swine/Korea/1204/2009; Sw/1204 (H1N2)] was virulent in ferrets, causing death within 10 d of inoculation, and was efficiently transmitted to naive contact ferrets via respiratory droplets. Although molecular analysis did not reveal known virulence markers, the Sw/1204 virus acquired mutations in hemagglutinin (HA) (Asp-225-Gly) and neuraminidase (NA) (Ser-315-Asn) proteins during the single ferret passage. The contact-Sw/1204 virus became more virulent in mice, replicated efficiently in vitro, extensively infected human lung tissues ex vivo, and maintained its ability to replicate and transmit in swine. Reverse-genetics studies further indicated that the HA225G and NA315N substitutions contributed substantially in altering virulence and transmissibility. These findings support the continuing threat of some field TRSw viruses to human and animal health, reviving concerns on the capacity of pigs to create future pandemic viruses. Apart from warranting continued and enhanced global surveillance, this study also provides evidence on the emerging roles of HA225G and NA315N as potential virulence markers in mammals.Keywords
This publication has 33 references indexed in Scilit:
- Avian-Type Receptor-Binding Ability Can Increase Influenza Virus Pathogenicity in MacaquesJournal of Virology, 2011
- Hemagglutinin–neuraminidase balance confers respiratory-droplet transmissibility of the pandemic H1N1 influenza virus in ferretsProceedings of the National Academy of Sciences, 2011
- Virulence and Genetic Compatibility of Polymerase Reassortant Viruses Derived from the Pandemic (H1N1) 2009 Influenza Virus and Circulating Influenza A VirusesJournal of Virology, 2011
- Altered Receptor Specificity and Cell Tropism of D222G Hemagglutinin Mutants Isolated from Fatal Cases of Pandemic A(H1N1) 2009 Influenza VirusJournal of Virology, 2010
- Virulence-Associated Substitution D222G in the Hemagglutinin of 2009 Pandemic Influenza A(H1N1) Virus Affects Receptor BindingJournal of Virology, 2010
- Mutations in the NS1 C-terminal tail do not enhance replication or virulence of the 2009 pandemic H1N1 influenza A virusJournal of General Virology, 2010
- Adaptive strategies of the influenza virus polymerase for replication in humansProceedings of the National Academy of Sciences, 2009
- Transmission and Pathogenesis of Swine-Origin 2009 A(H1N1) Influenza Viruses in Ferrets and MiceScience, 2009
- Antigenic and Genetic Characteristics of Swine-Origin 2009 A(H1N1) Influenza Viruses Circulating in HumansScience, 2009
- A DNA transfection system for generation of influenza A virus from eight plasmidsProceedings of the National Academy of Sciences of the United States of America, 2000