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Updated: May 31, 2026

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
08:32

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

Identification of DNA-damage DNA-binding protein 1 as a conditional essential factor for cytomegalovirus replication

Mirko Trilling1, Vu Thuy Khanh Le, Manuela Fiedler

  • 1Institute for Virology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.

Plos Pathogens
|June 24, 2011
PubMed

Insights

Mouse cytomegalovirus protein pM27 degrades STAT2 by recruiting host DDB1 protein, disrupting interferon signaling for viral replication. This mechanism is crucial for viral fitness in vivo.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Mouse cytomegalovirus (MCMV) protein pM27 is vital for viral fitness.
  • pM27 antagonizes interferon signal transduction mediated by signal transducer and activator of transcription 2 (STAT2).

Purpose of the Study:

  • To elucidate the molecular mechanism by which pM27 antagonizes STAT2-mediated interferon signaling.

Main Methods:

  • Investigated the effect of pM27 on STAT2 protein half-life.
  • Utilized proteasome inhibition and assessed STAT2 ubiquitination.
  • Examined pM27 interactions with host proteins, including DNA-damage DNA-binding protein (DDB) 1.
  • Employed truncation mutants of pM27 and siRNA-mediated knockdown of DDB1.
  • Assessed viral replication in interferon-conditioned cells.

Main Results:

  • pM27 significantly reduces STAT2 protein half-life.
  • Proteasome inhibition restores STAT2 levels and reveals poly-ubiquitinated STAT2.
  • pM27 directly interacts with DDB1, and this interaction is essential for STAT2 degradation.
  • Knockdown of DDB1 rescues STAT2 levels and impairs MCMV replication in interferon-treated cells.

Conclusions:

  • pM27 recruits the host ubiquitin ligase adaptor DDB1 to degrade STAT2.
  • This degradation process obstructs the STAT2-dependent antiviral state, promoting viral replication.
  • The pM27-DDB1-mediated degradation of STAT2 is a key mechanism for MCMV's in vivo fitness.

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