College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju 361-763, Republic of Korea.
Proc Natl Acad Sci U S A. 2012 Sep 25;109(39):15900-5. doi: 10.1073/pnas.1205576109. Epub 2012 Sep 10.
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.
迫切需要在全球范围内有效监测流感 A 病毒；2009 年新型重配大流行 H1N1（pH1N1）病毒的出现表明，猪可以成为大流行性流感的直接来源，必须监测猪群中流行病毒的大流行潜力。我们使用雪貂模型来评估与北美的株相关的主要韩国三重重配猪（TRSw）H1N2 和 H3N2 流感病毒的致病性和传染性。尽管大多数 TRSw 病毒的致病性中等，但有一种[猪/韩国/1204/2009；Sw/1204（H1N2）]在雪貂中具有毒力，接种后 10 天内导致死亡，并通过呼吸道飞沫有效地传播给未感染的接触雪貂。尽管分子分析未发现已知的毒力标记物，但 Sw/1204 病毒在单次雪貂传代过程中获得了血凝素（HA）（天冬氨酸 225-甘氨酸）和神经氨酸酶（NA）（丝氨酸 315-天冬酰胺）蛋白中的突变。接触 Sw/1204 病毒在小鼠中变得更具毒力，在体外有效地复制，广泛感染人肺组织，并且在猪中保持其复制和传播的能力。反向遗传学研究进一步表明，HA（225G）和 NA（315N）取代在改变毒力和传染性方面起着重要作用。这些发现支持了一些现场 TRSw 病毒对人类和动物健康的持续威胁，重新引起了人们对猪创造未来大流行病毒的能力的关注。除了保证持续和加强全球监测外，本研究还为 HA（225G）和 NA（315N）作为哺乳动物中潜在的毒力标记物的新作用提供了证据。
