Antibody prevents virus reactivation within the central nervous system.
The neurotropic JHM strain of mouse hepatitis virus (JHMV) produces an acute CNS infection characterized by encephalomyelitis and demyelination. The immune response cannot completely eliminate virus, resulting in persistence associated with chronic ongoing CNS demyelination. The contribution of humoral immunity to viral clearance and persistent infection was investigated in mice homozygous for disruption of the Ig mu gene (IgM-/-). Acute disease developed with equal kinetics and severity in IgM-/- and syngeneic C57BL/6 (wt) mice. However, clinical disease progressed in IgM-/- mice, while wt mice recovered. Viral clearance during acute infection was similar in both groups, supporting a primary role of cell-mediated immunity in viral clearance. In contrast to wt mice, in which infectious virus was reduced to below detection following acute infection, increasing infectious virus was recovered from the CNS of the IgM-/- mice following initial clearance. No evidence was obtained for selection of variant viruses nor was there an apparent loss of cell-mediated immunity in the absence of Ab. Passive transfer of anti-JHMV Ab following initial clearance prevented reactivation of infectious virus within the CNS of IgM-/- mice. These data demonstrate the clearance of infectious virus during acute disease by cell-mediated immunity. However, immunologic control is not maintained in the absence of anti-viral Ab, resulting in recrudescence of infectious virus. These data suggest that humoral immunity plays no role in controlling virus during acute infection, but plays an important role in establishing and maintaining CNS viral persistence.
Lin
M T
MT
Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033, USA.
Hinton
D R
DR
Marten
N W
NW
Bergmann
C C
CC
Stohlman
S A
SA
D000818:Animals; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000627:therapeutic use*; D018352:Coronavirus Infections / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D004679:Encephalomyelitis / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007116:Immunization, Passive; D007075:Immunoglobulin M / Q000172:deficiency / Q000235:genetics; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006517:Murine hepatitis virus / Q000254:growth & development*; D009500:Neutralization Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014775:Virus Activation / Q000276:immunology*
D000914:Antibodies, Viral; D007075:Immunoglobulin M