Ae. Matthews et al., Antibody is required for clearance of infectious murine hepatitis virus A59 from the central nervous system, but not the liver, J IMMUNOL, 167(9), 2001, pp. 5254-5263
Intracerebral inoculation with mouse hepatitis virus strain A59 results in
viral replication in the CNS and liver. To investigate whether B cells are
important for controlling mouse hepatitis virus strain A59 infection, we in
fected muMT mice who lack membrane-bound IgM and therefore mature B lymphoc
ytes. Infectious virus peaked and was cleared from the livers of muMT and w
ild-type mice. However, while virus was cleared from the CNS of wild-type m
ice, virus persisted in the CNS of muMT mice. To determine how B cells medi
ate viral clearance, we first assessed CD4(+) T cell activation in the abse
nce of B cells as APC. CD4+ T cells express wild-type levels of CD69 after
infection in muMT mice. IFN-gamma production in response to viral Ag in muM
T mice was also normal during acute infection, but was decreased 31 days po
stinfection compared with that in wild-type mice. The role of Ab in viral c
learance was also assessed. In wild-type mice plasma cells appeared in the
CNS around the time that virus is cleared. The muMT mice that received A59-
specific Ab had decreased virus, while mice with B cells deficient in Ab se
cretion did not clear virus from the CNS. Viral persistence was not detecte
d in FcR or complement knockout mice. These data suggest that clearance of
infectious mouse hepatitis virus strain A59 from the CNS requires Ab produc
tion and perhaps B cell support of T cells; however, virus is cleared from
the liver without the involvement of Abs or B cells.