title: Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses.
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 HA(225G) and NA(315N) 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 HA(225G) and NA(315N) as potential virulence markers in mammals.
authors.affiliation: College of Medicine and Medical Research Institute,  Chungbuk National University, Cheongju 361-763,  Republic of Korea.
authors.forename: Philippe Noriel Q
authors.initials: PN
authors.lastname: Pascua
authors.forename: Min-Suk
authors.initials: MS
authors.lastname: Song
authors.forename: Jun Han
authors.initials: JH
authors.lastname: Lee
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Baek
authors.forename: Hyeok-il
authors.initials: HI
authors.lastname: Kwon
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Eun Hye
authors.initials: EH
authors.lastname: Choi
authors.forename: Gyo-Jin
authors.initials: GJ
authors.lastname: Lim
authors.forename: Ok-Jun
authors.initials: OJ
authors.lastname: Lee
authors.forename: Si-Wook
authors.initials: SW
authors.lastname: Kim
authors.forename: Chul-Joong
authors.initials: CJ
authors.lastname: Kim
authors.forename: Moon Hee
authors.initials: MH
authors.lastname: Sung
authors.forename: Myung Hee
authors.initials: MH
authors.lastname: Kim
authors.forename: Sun-Woo
authors.initials: SW
authors.lastname: Yoon
authors.forename: Elena A
authors.initials: EA
authors.lastname: Govorkova
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Webby
authors.forename: Robert G
authors.initials: RG
authors.lastname: Webster
authors.forename: Young-Ki
authors.initials: YK
authors.lastname: Choi
mesh_terms: D000818:Animals; D002460:Cell Line; D004285:Dogs; D005289:Ferrets / Q000821:virology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D057221:Influenza A Virus, H1N2 Subtype / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D051379:Mice; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000635:transmission* / Q000662:veterinary*; D013552:Swine / Q000821:virology*; D013553:Swine Diseases; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D037521:Virulence Factors