tetano
Editor, Senior Moderator
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 RLO[SUP]1[/SUP], Gerhauser I[SUP]2[/SUP], Nehlmeier I[SUP]3[/SUP], G?rtner S[SUP]3[/SUP], Winkler M[SUP]3[/SUP], Leist SR[SUP]1,[/SUP][SUP]4[/SUP], Kollmus H[SUP]1[/SUP], P?hlmann S[SUP]3,[/SUP][SUP]5[/SUP], Schughart K[SUP]6,[/SUP][SUP]7,[/SUP][SUP]8[/SUP].
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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[SUP]-/-[/SUP] 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[SUP]-/-[/SUP] 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[SUP]-/-[/SUP] 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[SUP]-/-[/SUP] 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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H2 influenza A virus is not pathogenic in Tmprss2 knock-out mice.
Lambertz RLO[SUP]1[/SUP], Gerhauser I[SUP]2[/SUP], Nehlmeier I[SUP]3[/SUP], G?rtner S[SUP]3[/SUP], Winkler M[SUP]3[/SUP], Leist SR[SUP]1,[/SUP][SUP]4[/SUP], Kollmus H[SUP]1[/SUP], P?hlmann S[SUP]3,[/SUP][SUP]5[/SUP], Schughart K[SUP]6,[/SUP][SUP]7,[/SUP][SUP]8[/SUP].
Author information
Abstract
The host cell protease TMPRSS2 cleaves the influenza A virus (IAV) hemagglutinin (HA). Several reports have described resistance of Tmprss2[SUP]-/-[/SUP] 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[SUP]-/-[/SUP] 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[SUP]-/-[/SUP] 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[SUP]-/-[/SUP] 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
Free full text