Effects of PB1-F2 on the pathogenicity of H1N1 swine influenza virus in mice and pigs

文献类型： 外文期刊

第一作者： Lee, Jinhwa

作者： Lee, Jinhwa;Henningson, Jamie;Ma, Jingjiao;Duff, Michael;Lang, Yuekun;Li, Yonghai;Li, Yuhao;Nagy, Abdou;Sunwoo, Sunyoung;Bawa, Bhupinder;Yang, Jianmei;Bai, Dingping;Richt, Juergen A.;Ma, Wenjun;Yang, Jianmei;Bai, Dingping;Nagy, Abdou

作者机构：

关键词： PB1-F2;swine influenza H1N1 virus;pathogenicity;mouse and pig

期刊名称：JOURNAL OF GENERAL VIROLOGY （ 影响因子：3.891； 五年影响因子：3.719 ）

ISSN：

年卷期：

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收录情况： SCI

摘要： Although several studies have exploited the effects of PB1-F2 in swine influenza viruses, its contribution to the pathogenicity of swine influenza viruses remains unclear. Herein, we investigated the effects of PB1-F2 on the pathogenicity of influenza virus using a virulent H1N1 A/swine/Kansas/77778/2007 (KS07) virus, which expresses a full-length PB1-F2, in mice and pigs. Using reverse genetics, we generated the wild-type KS07 (KS07_WT), a PB1-F2 knockout mutant (KS07_ K/O) and its N66S variant (KS07_N66S). KS07_K/O showed similar pathogenicity in mice to the KS07_WT, whereas KS07_N66S displayed enhanced virulence when compared to the other two viruses. KS07_WT exhibited more efficient replication in lungs and nasal shedding in infected pigs than the other two viruses. Pigs infected with the KS07_WT had higher pulmonary levels of granulocyte-macrophage colony-stimulating factor, IFN-gamma, IL-6 and IL-8 at 3 and 5 days post-infection, as well as lower levels of IL-2, IL-4 and IL-12 at 1 day post-infection compared to those infected with the KS07_K/O. These results indicate that PB1-F2 modulates KS07 H1N1 virus replication, pathogenicity and innate immune responses in pigs and the single substitution at position 66 (N/S) in the PB1-F2 plays a critical role in virulence in mice. Taken together, our results provide new insights into the effects of PB1-F2 on the virulence of influenza virus in swine and support PB1-F2 as a virulence factor of influenza A virus in a strain-and host-dependent manner.

分类号： R37

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