Antibody is required for clearance of infectious murine hepatitis virus A59 from the central nervous system, but not the liver.
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 infected muMT mice who lack membrane-bound IgM and therefore mature B lymphocytes. Infectious virus peaked and was cleared from the livers of muMT and wild-type mice. However, while virus was cleared from the CNS of wild-type mice, virus persisted in the CNS of muMT mice. To determine how B cells mediate viral clearance, we first assessed CD4(+) T cell activation in the absence 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 muMT mice was also normal during acute infection, but was decreased 31 days postinfection compared with that in wild-type mice. The role of Ab in viral clearance 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 secretion did not clear virus from the CNS. Viral persistence was not detected in FcR or complement knockout mice. These data suggest that clearance of infectious mouse hepatitis virus strain A59 from the CNS requires Ab production and perhaps B cell support of T cells; however, virus is cleared from the liver without the involvement of Abs or B cells.
Matthews
A E
AE
Microbiology Department, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Weiss
S R
SR
Shlomchik
M J
MJ
Hannum
L G
LG
Gombold
J L
JL
Paterson
Y
Y
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D001921:Brain / Q000821:virology*; D005260:Female; D006508:Hepatitis Antibodies / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008099:Liver / Q000821:virology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D006517:Murine hepatitis virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D006508:Hepatitis Antibodies; D007371:Interferon-gamma