Autophagy induced by human adenovirus B7 structural protein VI inhibits viral replication

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Human adenovirus B7 (HAdV-B7) is a significant cause of severe acute lower respiratory tract infections in children.
• Current treatments and vaccines for HAdV-B7 are lacking, and its pathogenesis remains unclear.
• Autophagy is a critical innate immune process involved in viral clearance and immune response modulation.

Purpose of the Study:

• To investigate the role of autophagy in HAdV-B7 infection.
• To explore the potential of pharmacological autophagy induction as an antiviral strategy against HAdV-B7.
• To identify host factors involved in the autophagy-mediated restriction of HAdV-B7.

Main Methods:

• Assessing autophagic flux in HAdV-B7 infected cells.
• Evaluating the effect of autophagy-inducing drugs on viral replication.
• Identifying host-viral protein interactions using techniques like co-immunoprecipitation.

Main Results:

• HAdV-B7 infection successfully induced a complete autophagic flux in host cells.
• Pharmacological induction of autophagy significantly reduced HAdV-B7 replication.
• The host protein Bcl2-associated athanogene 3 (BAG3) was identified to mediate autophagy against HAdV-B7.
• BAG3 inhibits viral replication by interacting with the pVI protein's PPSY motif via its WW domain.

Conclusions:

• Autophagy plays a protective role against HAdV-B7 infection.
• Targeting autophagy, particularly through BAG3, presents a promising therapeutic avenue for HAdV-B7 infections.
• These findings contribute to understanding host-virus interactions and developing broad-spectrum anti-adenovirus therapies.