MATURE B-CELLS ARE REQUIRED FOR ACUTE SPLENIC INFECTION, BUT NOT FOR ESTABLISHMENT OF LATENCY, BY MURINE GAMMAHERPESVIRUS-68

Murine gammaherpesvirus 68 (gamma HV-68; also referred to as MHV-68) i s a gammaherpesvirus which infects murid rodents. Previous studies sho wed that CD8 T cells are important for controlling gamma HV-68 replica tion during the first 2 weeks of infection and suggested a role for B cells in latent or persistent gamma HV-68 infection, To further define the importance of B cells and CD8 T cells during acute and chronic ga mma HV-68 infection, we examined splenic infection in mice with null m utations in the transmembrane domain of the mu-heavy-chain constant re gion (MuMT; B-cell and antibody deficient) or in the beta(2)-microglob ulin gene (beta(2)(-/-); CD8 deficient), Immunocompetent mice infected intraperitoneally with gamma HV-68 demonstrated peak splenic titers 9 to 10 days postinfection, cleared infectious virus 15 to 20 days post infection, and harbored low levels of latent virus at 6 weeks postinfe ction, beta(2)(-/-) mice showed peak splenic gamma HV-68 titers simila r to those of normal mice but were unable to clear infectious virus co mpletely from the spleen, demonstrating persistent infectious virus 6 weeks postinfection. These data indicate that CD8 T cells are importan t for clearing infectious gamma HV-68 from the spleen. Infected MuMT m ice did not demonstrate detectable infectious gamma HV-68 in the splee n at any time after infection, indicating that mature B lymphocytes ar e necessary for acute splenic infection by gamma HV-68. Despite the la ck of measurable acute infection, MuMT spleen cells harbored latent vi rus 6 weeks postinfection at a level about 100-fold higher than that i n normal mice. These data demonstrate establishment of latency by a he rpesvirus in an organ in the absence of acute viral replication in tha t organ, In addition, they demonstrate that gamma HV-68 can establish latency in a cell type other than mature B lymphocytes.