Antibody Is Required for Clearance of Infectious Murine Hepatitis Virus A59 from the Central Nervous System, But Not the Liver

Abstract

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-γ 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.

Association Between Anticonvulsant Hypersensitivity Syndrome and Human Herpesvirus 6 Reactivation and Hypogammaglobulinemia

“…Surprisingly, B cells are required for the clearance of infectious virus from the central nervous system but not the liver, suggesting that the requirement for B cells in clearance of a viral infection can be organ specific. 37,38 Thus, these studies showing the importance of antibodies and B cells in controlling the persistent stage of viral infection are consistent with our data suggesting a contribution of serum IgG and B cells to prevent HHV-6 reactivation. However, these findings could alternatively be interpreted as indicating that decreased IgG production merely represents an early manifestation of AHS but not an etiologic factor.…”

B Cells and Antibody Play Critical Roles in the Immediate Defense of Disseminated Infection by West Nile Encephalitis Virus

“…Similarly, SCID mice developed high-grade viremia and CNS infection and succumbed to infection after inoculation with a candidate WNV vaccine strain (22). B cells and antibody have been proposed to protect against encephalitis caused by other flaviviruses (8,25,32,38) and non-flaviviruses (6,19,20,33,37,43,44,48). In some of these infection models (e.g., Sindbis, murine hepatitis, and lymphocytic choriomeningitis viruses), antibody and B cells contribute to the eradication of infection by clearing virus from the brain (19,29) or preventing viral recrudescence (6,43).…”

“…Passive administration of monoclonal antibodies (MAbs) limits the encephalitis caused by some flaviviruses (Saint Louis encephalitis [32,38], Japanese encephalitis [25], and yellow fever [7,40,41] viruses) and nonflaviviruses (Sindbis [19-21, 44, 48], murine hepatitis [6,33,37], and lymphocytic choriomeningitis [43] viruses). However, for many of these viruses the mechanism by which antibody attenuates CNS infection has not been clearly demonstrated.…”

CpG Oligodeoxynucleotides Protect Newborn Mice from a Lethal Challenge with the Neurotropic Tacaribe Arenavirus

“…More likely, the Abs are required for viral clearance as described for Sindbis virus (reviewed in Ref. 50) and the mouse hepatitis virus (34), two virus models where the Abs help control virus replication in CNS. Of note, sera is known to exert immunoregulatory effects independent from the presence of Ag-specific Abs, such as the Fc receptordependent induction of anti-inflammatory cytokines (51,52).…”

“…To confirm that the Ab response induced by CpG ODN treatment is required for CpG ODN-mediated immunoprotection, newborn MT KO mice, which lack developmentally mature B cells, were infected with TCRV (34,35). These mice died despite CpG ODN treatment but could be rescued when treated with sera from convalescent mice (Fig.…”