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

[tetano]

Virol J. 2020 Apr 22;17(1):56. doi: 10.1186/s12985-020-01323-z.
H2 influenza A virus is not pathogenic in Tmprss2 knock-out mice.


Lambertz RLO¹, Gerhauser I², Nehlmeier I³, G?rtner S³, Winkler M³, Leist SR^1,4, Kollmus H¹, P?hlmann S^3,5, Schughart K^6,7,8.

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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.



KEYWORDS:

H2 subtype; Host protease; Influenza a virus; Mouse mutant; TMPRSS2


PMID:32321537DOI:10.1186/s12985-020-01323-z
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