Rb-E2F-HDAC Repressor Complexes Control Interferon-Induced Repression of Adenovirus To Promote Persistent Infection

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Interferons (IFNs) are crucial for antiviral immunity.
• Human adenovirus (HAdV) can establish persistent infections.
• The mechanisms of HAdV persistence are not fully understood.

Purpose of the Study:

• To elucidate the host cell mechanisms underlying IFN-mediated persistent HAdV infection.
• To identify host factors involved in HAdV persistence.

Main Methods:

• Investigated the role of IFN signaling in HAdV persistence.
• Assessed the impact of retinoblastoma (Rb) family proteins and cyclin-dependent kinase 4 (CDK4) on viral repression.
• Examined the effect of histone deacetylase (HDAC) inhibitors on persistently infected cells.

Main Results:

• IFN signaling is essential for viral repression and promoting persistent infection.
• CDK4 disrupts IFN-induced viral repression; knockout of Rb family proteins reduces IFN's effect.
• HDAC inhibitors activate productive viral replication in persistently infected cells, indicating HDACs' role in maintaining persistence.
• An Rb-E2F-HDAC repressor complex inhibits HAdV-C5 productive infection.

Conclusions:

• pRb and class I HDACs are critical for the IFN-induced repressor complex that promotes HAdV persistence.
• HDAC inhibition can convert persistent HAdV infection to a lytic infection.
• This study reveals the noncanonical regulation of Rb-E2F signaling in persistent HAdV infections.