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Human cytomegalovirus UL69 protein facilitates translation by associating with the mRNA cap-binding complex and

Mariko Aoyagi1, Miguel Gaspar, Thomas E Shenk

  • 1Department of Molecular Biology, Princeton University, Princeton, NJ 08540, USA.

Proceedings of the National Academy of Sciences of the United States of America
|February 6, 2010
PubMed

Insights

Human cytomegalovirus uses protein pUL69 to support translation by excluding hypophosphorylated 4EBP1 from the mRNA cap-binding complex, ensuring viral protein production during infection.

Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Biology

Background:

  • Translation regulation is crucial for cellular processes.
  • The mTORC1 pathway and 4EBP1 protein are key regulators of translation.
  • Human cytomegalovirus (HCMV) manipulates host cell machinery for its replication.

Purpose of the Study:

  • To investigate the role of HCMV protein pUL69 in translation regulation.
  • To elucidate the mechanism by which pUL69 antagonizes 4EBP1 activity.
  • To understand how HCMV ensures efficient protein synthesis during infection.

Main Methods:

  • Co-immunoprecipitation assays to detect protein interactions.
  • Analysis of protein complex composition during viral infection.
  • Western blotting to assess protein phosphorylation states.

Main Results:

  • HCMV pUL69 protein interacts with eIF4A1 and poly(A)-binding protein.
  • During wild-type HCMV infection, pUL69 excludes 4EBP1 from the cap-binding complex.
  • Infection with pUL69-deficient HCMV results in 4EBP1 presence in the complex and reduced late viral protein accumulation.

Conclusions:

  • HCMV pUL69 antagonizes 4EBP1 by a distinct mechanism compared to pUL38.
  • pUL69 supports viral translation by preventing hypophosphorylated 4EBP1 from inhibiting the cap-binding complex.
  • This mechanism is essential for efficient production of late viral proteins in HCMV-infected cells.

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