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

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Human adenoviruses (HAdV) recruit the HBO1 histone acetyltransferase complex for replication. Downregulating HBO1 reduces viral gene expression and HAdV5 growth by affecting histone acetylation at viral promoters.

Keywords:
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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.