H2 influenza A virus is not pathogenic in Tmprss2 knock-out mice

Ruth Lydia Olga Lambertz,Ingo Gerhauser,Stefan Pöhlmann,Michael Winkler,Inga Nehlmeier,Klaus Schughart,Sarah Rebecca Leist,Heike Kollmus,Sabine Gärtner

doi:10.1186/s12985-020-01323-z

Abstract

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.

Highlights

The hemagglutinin (HA) of influenza A virus (IAV) facilitates viral entry into target cells
Our studies showed that infected Tmprss2−/− mice exhibited a significant seroconversion that was similar to infected wild type (WT) mice (Fig. 5)
We showed that Tmprss2−/− mice were resistant to H2 IAV pathogenesis

Summary

Introduction

The hemagglutinin (HA) of influenza A virus (IAV) facilitates viral entry into target cells. Viral replication in lungs of infected (dose of 2 × 104 ffu) female Tmprss2−/− and WT mice (8–12 weeks old) revealed no detectable virus replication in Tmprss2−/− mice, whereas WT mice showed increased lung titers at day 2 and 4 post infection (dpi) (Fig. 2c). We performed histopathological studies on tissue sections from PR8_HA(H2) infected Tmprss2−/− and WT mice (Fig. 3).

Results

Conclusion