MHV infection of the CNS: mechanisms of immune-mediated control.
Mice infected with neurotropic strains of mouse hepatitis virus (MHV) clear infectious virus; nevertheless, viral persistence in the central nervous system (CNS) is associated with ongoing primary demyelination. Acute infection induces a potent regional CD8+ T-cell response. The high prevalence of virus specific T cells correlates with ex vivo cytolytic activity, interferon-gamma (IFN-gamma) secretion and efficient reduction in virus. Viral clearance from most cell types is controlled by a perforin dependent mechanism. However, IFN-gamma is essential for controlling virus replication in oligodendrocytes. Furthermore, CD4+ T cells enhance CD8+ T-cell survival and effectiveness. Clearance of infectious virus is associated with a gradual decline of CNS T cells; nevertheless, activated T cells are retained within the CNS. The loss of cytolytic activity, but retention of IFN-gamma secretion during viral clearance suggests stringent regulation of CD8+ T-cell effector function, possibly as a means to minimize CNS damage. However, similar CD8+ T-cell responses to demyelinating and non demyelinating JHMV variants support the notion that CD8+ T cells do not contribute to the demyelinating process. Although T-cell retention is tightly linked to the presence of persisting virus, contributions to regulating the latent state are unknown. Studies in B-cell-deficient mice suggest that antibodies are required to prevent virus recrudescence. Although acute JHMV infection is thus primarily controlled by CD8+ T cells, both CD4+ T cells and B cells make significant contributions in maintaining the balance between viral replication and immune control, thus allowing host and pathogen survival.
Department of Pathology, University of Southern California, Keck School of Medicine, Los Angeles 90033, USA. marten@hsc.usc.edu
N W
NW
Marten
S A
SA
Stohlman
C C
CC
Bergmann
D000818:Animals; D002494:Central Nervous System Infections / Q000276:immunology* / Q000821:virology; D018352:Coronavirus Infections / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D006517:Murine hepatitis virus / Q000276:immunology*