HBO1/KAT7/MYST2 HAT complex regulates human adenovirus replicative cycle

Area of Science:

• Virology
• Molecular Biology
• Epigenetics

Background:

• Human adenoviruses (HAdV) are DNA tumor viruses that utilize cellular machinery for replication.
• Understanding viral hijacking of host cell processes is key to virology research.
• HBO1 (Histone Acetyltransferase Binding to ORC1) is a histone acetyltransferase complex involved in cell proliferation.

Purpose of the Study:

• To investigate the role of HBO1 in human adenovirus type 5 (HAdV5) replication.
• To determine if HBO1 influences viral gene expression and histone acetylation during infection.

Main Methods:

• Downregulation of HBO1 in human cells followed by HAdV5 infection.
• Analysis of viral early gene expression (e.g., E1A).
• Assessment of H3 lysine 14 acetylation at viral promoters using ChIP.
• Detection of HBO1 association with viral promoters and replication centers.
• Co-immunoprecipitation assays to study E1A and HBO1 interaction.

Main Results:

• HBO1 downregulation significantly reduced HAdV5 growth and early viral gene expression.
• Reduced H3 lysine 14 acetylation at viral promoters was observed in HBO1-downregulated cells.
• HBO1 was found associated with viral promoters and co-localized with viral replication centers.
• Overexpression of E1A stimulated HBO1 activity and E1A co-immunoprecipitated with HBO1.

Conclusions:

• HAdV5 actively recruits the HBO1 HAT complex to facilitate viral replication.
• HBO1 plays a critical role in promoting viral gene expression through histone acetylation at viral promoters.
• The interaction between HAdV and HBO1 highlights a novel mechanism of viral exploitation of host epigenetic machinery.