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Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
11:28

Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus

Published on: October 7, 2011

Major human cytomegalovirus structural protein pp65 (ppUL83) prevents interferon response factor 3 activation in the

Davide A Abate1, Shinya Watanabe, Edward S Mocarski

  • 1Department of Microbiology and Immunology, D 347 Fairchild Science Bldg., Stanford University School of Medicine, Stanford, CA 94305-5124, USA.

Journal of Virology
|September 29, 2004
PubMed

Insights

Human cytomegalovirus uses its major structural protein, pp65, to block the interferon response. This protein inhibits interferon response factor 3 (IRF-3) activation, helping the virus evade immune detection.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Cellular responses to viral infection are critical for innate immunity.
  • Interferon production is a key component of the antiviral state.
  • Cytomegalovirus (CMV) has evolved mechanisms to evade host defenses.

Purpose of the Study:

  • To identify viral proteins involved in modulating the early interferon-like response to CMV infection.
  • To elucidate the mechanism by which CMV counteracts host antiviral defenses.

Main Methods:

  • Functional genomics screening to identify CMV proteins impacting cellular responses.
  • Analysis of host transcription factors, including IRF-3, NF-kappaB, STAT1, and STAT3.
  • Investigating the role of the pp65 (ppUL83) protein in IRF-3 regulation.

Main Results:

  • The major CMV structural protein, pp65 (ppUL83), was identified as a key modulator of the interferon response.
  • pp65 specifically inhibits the activation and nuclear accumulation of interferon response factor 3 (IRF-3).
  • IRF-3 phosphorylation is reduced in the presence of pp65, while NF-kappaB activation is unaffected.

Conclusions:

  • CMV utilizes its pp65 protein to actively suppress the IRF-3-mediated type I interferon response.
  • By inhibiting IRF-3, CMV evades a critical host alarm system for antiviral control and immune regulation.
  • This mechanism highlights how viral structural proteins can play direct roles in immune evasion.

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