H2 influenza A virus is not pathogenic in Tmprss2 knock-out mice
H2 influenza A virus is not pathogenic in Tmprss2 knock-out mice
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DOI：
10.1186/s12985-020-01323-z
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发表时间：
2020-04-22
期刊：
影响因子：
4.8
通讯作者：
Schughart, Klaus
中科院分区：
文献类型：
--
作者：
Lambertz, Ruth Lydia Olga;Gerhauser, Ingo;Schughart, Klaus
宿主细胞蛋白酶TMPRSS 2切割甲型流感病毒（IAV）血凝素（HA）。一些报道已经描述了Tmprss 2（-/-）敲除（KO）小鼠对IAV感染的抗性，但是H2亚型的IAV尚未被检测。在这里，我们证明了TMPRSS 2能够在细胞培养物中切割H2-HA，并且Tmprss 2（-/-）小鼠对重新分类的PR8_HA（H2）病毒的感染具有抗性。KO小鼠的感染没有引起主要的体重减轻或死亡。此外，在Tmprss 2（-/-）小鼠中未观察到肺重量显著增加和病毒复制。最后，仅检测到轻微的组织损伤和免疫细胞浸润，在Tmprss 2（-/-）小鼠的组织切片中未发现病毒阳性细胞。总之，我们的研究表明，TMPRSS 2是H2 IAV在小鼠中传播和发病所必需的。这些发现扩展了先前的结果，指出TMPRSS 2在IAV感染中的核心作用，并验证宿主蛋白酶作为抗病毒治疗的潜在靶点。
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.