Antibody prevents virus reactivation within the central nervous system

The neurotropic JHM strain of mouse hepatitis virus (JHMV) produces an acut e CNS infection characterized by encephalomyelitis and demyelination. The i mmune response cannot completely eliminate virus, resulting in persistence associated with chronic ongoing CNS demyelination, The contribution of humo ral immunity to viral clearance and persistent infection was investigated i n mice homozygous for disruption of the Ig mu gene (IgM(-/-)). Acute diseas e developed with equal kinetics and severity in IgM(-/-) and syngeneic C57B L/6 (wt) mice. However, clinical disease progressed in IgM(-/-) mice, while wt mice recovered. Viral clearance during acute infection was similar in b oth groups, supporting a primary role of cell-mediated immunity in viral cl earance. In contrast to wt mice, in which infectious virus was reduced to b elow detection following acute infection, increasing infectious virus was r ecovered from the CNS of. the IgM(-/-) mice following initial clearance. No evidence was:obtained for selection of variant viruses nor was there an::a pparent loss of cell-mediated immunity in the absence of Ab, Passive transf er of anti-JHMV Ab following initial clearance prevented reactivation of in fectious virus within the CNS: of IgM(-/-) mice. These data demonstrate the clearance of infectious virus during acute disease by cell-mediated immuni ty. However, immunologic control is not maintained in the absence of anti-v iral Ab, resulting in recrudescence of infectious virus. These data Suggest that humoral immunity plays no role in controlling virus during acute infe ction,but, plays an important role in establishing and maintaining CNS vira l persistence.