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

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• The host cell protease TMPRSS2 (transmembrane serine protease 2) cleaves hemagglutinin (HA) of influenza A virus (IAV).
• Tmprss2 knockout (KO) mice exhibit resistance to certain IAV infections, but H2 subtype IAV has not been studied.
• TMPRSS2's role in cleaving H2-HA and its impact on H2 IAV pathogenesis remain unclear.

Purpose of the Study:

• To investigate the role of TMPRSS2 in cleaving H2-HA.
• To determine the susceptibility of Tmprss2 knockout mice to H2 IAV infection.
• To evaluate the therapeutic potential of targeting TMPRSS2 for H2 IAV.

Main Methods:

• Cell culture experiments to assess TMPRSS2 cleavage of H2-HA.
• Infection of Tmprss2 knockout mice with a re-assorted PR8 virus expressing H2-HA.
• Assessment of clinical signs, viral replication, lung pathology, and immune cell infiltration in infected mice.

Main Results:

• TMPRSS2 effectively cleaves H2-HA in cell culture.
• Tmprss2 knockout mice were resistant to H2 IAV infection, showing no significant weight loss or mortality.
• No significant lung weight increase, viral replication, or substantial tissue damage was observed in knockout mice.

Conclusions:

• TMPRSS2 is crucial for the spread and pathogenesis of H2 IAV in mice.
• These findings confirm the essential role of TMPRSS2 in IAV infections.
• Host proteases like TMPRSS2 represent a promising target for developing novel antiviral therapies against influenza viruses.