The SFTSV Nonstructural Proteins Induce Autophagy to Promote Viral Replication via Interaction with Vimentin

Area of Science:

• Virology
• Cellular Biology
• Immunology

Background:

• Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne phlebovirus causing severe illness.
• SFTSV nucleoprotein (N) is known to induce autophagy, but other viral proteins' roles are unclear.
• Autophagy plays a complex role in viral infections and host immune responses.

Purpose of the Study:

• To investigate the role of SFTSV nonstructural protein NSs in regulating autophagy.
• To elucidate the mechanism by which SFTSV NSs induces autophagy.
• To identify potential antiviral targets for SFTSV.

Main Methods:

• Identified SFTSV NSs as the viral component mediating autophagy induction.
• Investigated the interaction between SFTSV NSs and host vimentin.
• Analyzed vimentin degradation via the ubiquitin-proteasome pathway.
• Assessed the impact of vimentin overexpression on autophagy and viral replication.

Main Results:

• SFTSV NSs induces autophagy independently of inclusion bodies.
• NSs interacts with vimentin, leading to its K48-linked ubiquitination and degradation.
• This NSs-vimentin interaction inhibits Beclin1-vimentin complex formation, promoting autophagy.
• Vimentin overexpression antagonizes NSs-induced autophagy and inhibits SFTSV replication.

Conclusions:

• SFTSV NSs activates autophagy through a novel mechanism involving vimentin degradation.
• Vimentin is a key host factor regulated by SFTSV NSs and serves as a potential antiviral target.
• Understanding NSs function provides insights into SFTSV pathogenesis and potential therapeutic strategies.