ILDR1 promotes influenza A virus replication through binding to PLSCR1

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Phospholipid scramblase 1 (PLSCR1) is a natural antiviral regulator that inhibits influenza A virus (IAV) replication in cells.
• The in vivo antiviral function and regulatory mechanisms of PLSCR1 against IAV remain largely unexamined.

Purpose of the Study:

• To investigate the in vivo antiviral role of PLSCR1 against H1N1 swine influenza virus (SIV).
• To identify novel PLSCR1-interacting proteins and elucidate the underlying regulatory mechanism of IAV infection.

Main Methods:

• Yeast two-hybrid screening was employed to identify PLSCR1-binding partners.
• Expression levels of PLSCR1 and ILDR1 were analyzed in infected mouse models.
• Protein-protein interactions were confirmed through binding assays.

Main Results:

• PLSCR1 expression decreased in H1N1 SIV-infected mice, with Plscr1 knockout mice showing increased susceptibility.
• Immunoglobulin-like domain-containing receptor 1 (ILDR1) was identified as a novel PLSCR1-binding partner.
• ILDR1, highly expressed in lungs and upregulated post-infection, competitively binds PLSCR1, not viral NP directly.

Conclusions:

• A novel PLSCR1-ILDR1-NP regulatory pathway is identified, crucial for limiting IAV infection.
• This pathway offers new insights into IAV-host interactions and potential therapeutic targets.