Sorting Nexin 10 Mediates Endosomal Acidification and Autophagy to Promote Influenza A Virus Infection

Area of Science:

• Virology
• Cell Biology
• Immunology

Background:

• Influenza A Virus (IAV) infection relies on host factors for replication.
• Sorting Nexin 10 (SNX10) regulates membrane trafficking and endosomal stabilization.
• Previous research linked SNX10 to human coronavirus OC43 replication via endocytosis.

Purpose of the Study:

• To investigate the role of SNX10 in Influenza A Virus (IAV) infection.
• To elucidate the molecular mechanisms by which SNX10 influences IAV replication.
• To evaluate SNX10 as a potential antiviral drug target.

Main Methods:

• Investigated SNX10's role in IAV infection using cell culture models.
• Utilized conditional knockout mice (Snx10) to assess survival post-IAV challenge.
• Examined SNX10's interaction with IAV proteins (NP and M2).
• Analyzed the impact of SNX10 on endosomal vesicle production and autophagy.

Main Results:

• SNX10 significantly promoted IAV infection in host cells.
• Conditional knockout of Snx10 in mice improved survival after IAV infection.
• SNX10 facilitates IAV replication by promoting acidic endosomal vesicles and pro-viral autophagic structures.
• SNX10 interacts with IAV NP and M2 proteins.
• Blocking SNX10-mediated pathways showed antiviral effects.
• IAV infection increases SNX10 protein levels by reducing its ubiquitination.

Conclusions:

• SNX10 is a crucial host factor that enhances Influenza A Virus replication.
• SNX10's interaction with viral proteins and its role in endosomal trafficking are key mechanisms.
• Targeting SNX10-mediated processes presents a promising host-directed antiviral strategy against IAV.