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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

Reovirus infection activates JNK and the JNK-dependent transcription factor c-Jun

P Clarke1, S M Meintzer, C Widmann

  • 1Departments of Neurology, University of Colorado Health Science Center, Denver, Colorado 80262, USA.

Journal of Virology
|November 2, 2001
PubMed

Insights

Reovirus infection activates specific host cell signaling pathways, particularly c-Jun N-terminal kinase (JNK), leading to increased c-Jun phosphorylation and apoptosis. Strain differences in JNK activation correlate with viral gene segments encoding outer capsid proteins.

Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Viral infections frequently disrupt host cell signaling pathways, including mitogen-activated protein kinases (MAPKs).
  • Understanding these disruptions is crucial for deciphering viral pathogenesis and host responses.

Purpose of the Study:

  • To investigate the specific mitogen-activated protein kinase (MAPK) pathways affected by reovirus infection.
  • To determine the correlation between viral strain, host cell signaling activation, and apoptosis.
  • To identify the viral genetic determinants responsible for strain-specific signaling pathway activation.

Main Methods:

  • Analysis of reovirus-infected host cells to measure mitogen-activated protein kinase (MAPK) activation, specifically c-Jun N-terminal kinase (JNK) and extracellular signal-related kinase (ERK).
  • Quantification of c-Jun phosphorylation, a downstream target of JNK.
  • Assessment of apoptosis induction in infected cells.
  • Utilizing reassortant reoviruses to map viral gene segments responsible for observed phenotypes.

Main Results:

  • Reovirus infection selectively activates c-Jun N-terminal kinase (JNK) and increases phosphorylation of its target, c-Jun.
  • Reovirus serotype 3 strains (T3A, T3D) induce significantly higher JNK activation, c-Jun phosphorylation, and apoptosis compared to serotype 1 (T1L).
  • Viral S1 and M2 gene segments, encoding outer capsid proteins sigma1 and mu1c, determine strain-specific JNK activation and apoptosis.
  • Extracellular signal-related kinase (ERK) is also activated in a strain-specific manner, but its activation could not be mapped to specific viral gene segments.

Conclusions:

  • Reovirus infection triggers distinct host cell signaling responses, notably JNK pathway activation, which correlates with apoptosis.
  • Strain-specific differences in JNK activation and apoptosis are linked to viral outer capsid proteins encoded by S1 and M2 gene segments.
  • Apoptosis and c-Jun phosphorylation occur via parallel pathways, with apoptosis partially modulated by TRAIL/receptor interactions, while JNK activation is independent of this.

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