%0 Journal Article %A Lee, Jinhwa %A Henningson, Jamie %A Ma, Jingjiao %A Duff, Michael %A Lang, Yuekun %A Li, Yonghai %A Li, Yuhao %A Nagy, Abdou %A Sunwoo, Sunyoung %A Bawa, Bhupinder %A Yang, Jianmei %A Bai, Dingping %A Richt, Juergen A. %A Ma, Wenjun %T Effects of PB1-F2 on the pathogenicity of H1N1 swine influenza virus in mice and pigs %D 2017 %J Journal of General Virology, %V 98 %N 1 %P 31-42 %@ 1465-2099 %R https://doi.org/10.1099/jgv.0.000695 %K pathogenicity %K swine influenza H1N1 virus %K PB1-F2 %K mouse and pig %I Microbiology Society, %X 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-γ, 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. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.000695