Pathogenesis of acute and chronic central nervous system infection with variants of mouse hepatitis virus, strain JHM.
Infection of mice with variants of mouse hepatitis virus, strain JHM (MHV-JHM), provide models of acute and chronic viral infection of the central nervous system (CNS). Through targeted recombination and reverse genetic manipulation, studies of infection with MHV-JHM variants have identified phenotypic differences and examined the effects of these differences on viral pathogenesis and anti-viral host immune responses. Studies employing recombinant viruses with a modified spike (S) glycoprotein of MHV-JHM have identified the S gene as a major determinant of neurovirulence. However, the association of S gene variation and neurovirulence with host ability to generate anti-viral CD8 T cell responses is not completely clear. Partially protective anti-viral immune responses may result in persistent infection and chronic demyelinating disease characterized by myelin removal from axons of the CNS and associated with dense macrophage/microglial infiltration. Demyelinating disease during MHV-JHM infection is immune-mediated, as mice that lack T lymphocytes fail to develop disease despite succumbing to encephalitis with high levels of infectious virus in the CNS. However, the presence of T lymphocytes or anti-viral antibody can induce disease in infected immunodeficient mice. The mechanisms by which these immune effectors induce demyelination share an ability to activate and recruit macrophages and microglia, thus increasing the putative role of these cells in myelin destruction.
Templeton
Steven P
SP
Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242, USA.
Perlman
Stanley
S
D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D020805:Central Nervous System Viral Diseases / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D018925:Chemokines / Q000276:immunology / Q000378:metabolism; D002908:Chronic Disease; D018352:Coronavirus Infections / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D003711:Demyelinating Diseases / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D051379:Mice; D006517:Murine hepatitis virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D014774:Virulence
D018925:Chemokines