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MHV infection of the CNS: mechanisms of immune-mediated control

N W Marten1, S A Stohlman, C C Bergmann

  • 1Department of Pathology, University of Southern California, Keck School of Medicine, Los Angeles 90033, USA. marten@hsc.usc.edu

Viral Immunology
|March 29, 2001
PubMed

Insights

Mouse hepatitis virus (MHV) infection in mice involves CD8+ T cells controlling viral clearance, while CD4+ T cells and B cells aid in long-term immune balance. This immune response prevents viral recrudescence in the central nervous system (CNS).

Area of Science:

  • Neurovirology
  • Immunology
  • Central Nervous System (CNS) Research

Background:

  • Neurotropic mouse hepatitis virus (MHV) infection causes viral persistence and demyelination in the CNS despite infectious virus clearance.
  • Acute MHV infection elicits a strong CD8+ T-cell response crucial for viral reduction, with interferon-gamma (IFN-gamma) essential for oligodendrocyte control.

Purpose of the Study:

  • To investigate the role of T cells and B cells in controlling MHV infection and demyelination within the CNS.
  • To understand the regulation of CD8+ T-cell effector functions during viral clearance and persistence.

Main Methods:

  • Infection of mice with neurotropic MHV strains.
  • Analysis of CD8+ and CD4+ T-cell responses, including cytolytic activity and IFN-gamma secretion.
  • Assessment of viral clearance mechanisms, including perforin-dependent pathways.
  • Studies utilizing B-cell-deficient mice to evaluate antibody roles.

Main Results:

  • CD8+ T cells are vital for clearing infectious MHV, utilizing perforin-dependent mechanisms and IFN-gamma for oligodendrocyte protection.
  • While CD8+ T-cell cytolytic activity diminishes, IFN-gamma secretion is retained during viral clearance, suggesting regulated immune responses.
  • CD4+ T cells support CD8+ T-cell survival, and antibodies are necessary to prevent viral recrudescence.
  • CD8+ T cells do not appear to directly contribute to the demyelinating process.

Conclusions:

  • Acute MHV infection is primarily controlled by CD8+ T cells, with crucial support from CD4+ T cells and B cells.
  • Immune cells, particularly T cells, are retained in the CNS, contributing to the balance between viral persistence and immune control.
  • Antibodies play a key role in preventing viral recrudescence, ensuring host and pathogen survival.

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