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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

Amplification of JNK signaling is necessary to complete the murine gammaherpesvirus 68 lytic replication cycle

James A Stahl1, Clinton R Paden, Shweta S Chavan

  • 1Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.

Journal of Virology
|September 28, 2012
PubMed

Insights

Murine gammaherpesvirus 68 (MHV68) hijacks host cell signaling by activating JNK/c-Jun pathways during late infection stages. This host cell signaling is crucial for productive viral replication and gene expression.

Area of Science:

  • Virology
  • Cellular Signaling
  • Molecular Biology

Background:

  • Host-derived signaling pathways are known to influence gammaherpesvirus replication.
  • Pathways regulating later stages of productive gammaherpesvirus replication remain poorly understood.

Purpose of the Study:

  • To identify host cell phosphoproteins involved in late stages of lytic murine gammaherpesvirus 68 (MHV68) infection.
  • To elucidate the role of identified host factors in the viral replication cycle.

Main Methods:

  • Mass spectrometry was employed to identify cellular phosphoproteins during MHV68 infection.
  • Kinetic analysis of protein phosphorylation and transcription factor activation was performed.
  • Pharmacologic and dominant-negative inhibition of specific signaling molecules (JNK1/2) were used to assess their impact on viral replication.

Main Results:

  • c-Jun was identified as an abundant cellular phosphoprotein during late stages of MHV68 infection.
  • Increased phosphorylation of c-Jun, JNK1/2, and AP-1 activation correlated with MHV68 infection progression.
  • JNK1/2 inhibition significantly impaired viral DNA synthesis, viral gene expression, and overall viral replication.
  • These signaling events were independent of viral DNA replication but dependent on progression beyond immediate-early gene expression.

Conclusions:

  • MHV68 usurps and amplifies host JNK/c-Jun signaling during late infection stages.
  • This host signaling pathway is essential for facilitating late stages of the MHV68 lytic replication cycle.
  • Targeting JNK/c-Jun signaling represents a potential strategy to inhibit MHV68 productive infection.

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