The host cell protease TMPRSS2 cleaves the influenza A virus (IAV) hemagglutinin (HA). Several reports have described resistance of Tmprss2-/- knock-out (KO) mice to IAV infection but IAV of the H2 subtype have not been examined yet. Here, we demonstrate that TMPRSS2 is able to cleave H2-HA in cell culture and that Tmprss2-/- mice are resistant to infection with a re-assorted PR8_HA(H2) virus. Infection of KO mice did not cause major body weight loss or death. Furthermore, no significant increase in lung weights and no virus replication were observed in Tmprss2-/- mice. Finally, only minor tissue damage and infiltration of immune cells were detected and no virus-positive cells were found in histological sections of Tmprss2-/- mice. In summary, our studies indicate that TMPRSS2 is required for H2 IAV spread and pathogenesis in mice. These findings extend previous results pointing towards a central role of TMPRSS2 in IAV infection and validate host proteases as a potential target for antiviral therapy.

中文翻译：

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H2甲型流感病毒在Tmprss2基因敲除小鼠中没有致病性。

宿主细胞蛋白酶TMPRSS2切割甲型流感病毒（IAV）血凝素（HA）。几篇报道描述了Tmprss2-/-敲除（KO）小鼠对IAV感染的抗性，但尚未检查H2亚型的IAV。在这里，我们证明了TMPRSS2能够在细胞培养物中裂解H2-HA，并且Tmprss2-/-小鼠对重组PR8_HA（H2）病毒的感染具有抵抗力。KO小鼠的感染没有引起体重的减轻或死亡。此外，在Tmprss2-/-小鼠中未观察到肺重量的显着增加和病毒复制。最后，在Tmprss2-/-小鼠的组织学切片中仅检测到较小的组织损伤和免疫细胞浸润，未发现病毒阳性细胞。总而言之，我们的研究表明TMPRSS2是小鼠H2 IAV传播和发病机理所必需的。