HDAC6 Facilitates PRV and VSV Infection by Inhibiting Type I Interferon Production

Area of Science:

• Virology
• Immunology
• Molecular Biology

Background:

• Histone deacetylase 6 (HDAC6) is implicated in various cellular processes, including viral infection.
• Understanding HDAC6's role in host-pathogen interactions is crucial for developing antiviral strategies.

Purpose of the Study:

• To investigate the role of HDAC6 in modulating viral infection in pig cells.
• To identify potential antiviral gene targets in pigs based on HDAC6 function.

Main Methods:

• Gene knockout and overexpression strategies were employed in PK15 pig cells.
• Viral infectivity assays were performed for Pseudorabies virus (PRV) and Vesicular stomatitis virus (VSV).
• Mechanistic studies focused on DNA damage and type I Interferon (IFN) production.

Main Results:

• HDAC6 knockout significantly reduced PRV and VSV infectivity in PK15 cells.
• HDAC6 overexpression enhanced PRV and VSV infectivity.
• HDAC6 was identified as a DNA damage inhibitor; its overexpression attenuated DNA damage and type I IFN production, promoting viral infection.
• HDAC6 deficiency increased DNA damage and type I IFN production, limiting viral infection.

Conclusions:

• HDAC6 plays a critical role in modulating the infectivity of multiple viruses in pig cells.
• HDAC6 influences viral infection by regulating DNA damage and type I IFN production, linking host immune response to viral load.
• Targeting HDAC6 presents a potential strategy for antiviral interventions in pigs.