Mature B cells are required for acute splenic infection, but not for establishment of latency, by murine gammaherpesvirus 68

Murine gammaherpesvirus 68 (γHV-68; also referred to as MHV-68) is a gammaherpesvirus which infects murid rodents. Previous studies showed that CD8 T cells are important for controlling γHV-68 replication during the first 2 weeks of infection and suggested a role for B cells in latent or persistent γHV-68 infection. To further define the importance of B cells and CD8 T cells during acute and chronic γHV-68 infection, we examined splenic infection in mice with null mutations in the transmembrane domain of the μ- heavy-chain constant region (MuMT; B-cell and antibody deficient) or in the β₂-microglobulin gene (β₂(-/-); CD8 deficient). Immunocompetent mice infected intraperitoneally with γHV-68 demonstrated peak splenic titers 9 to 10 days postinfection, cleared infectious virus 15 to 20 days postinfection, and harbored low levels of latent virus at 6 weeks postinfection. β₂(-/-) mice showed peak splenic γHV-68 titers similar to those of normal mice but were unable to clear infectious virus completely from the spleen, demonstrating persistent infectious virus 6 weeks postinfection. These data indicate that CD8 T cells are important for clearing infectious γHV-68 from the spleen. Infected MuMT mice did not demonstrate detectable infectious γHV-68 in the spleen at any time after infection, indicating that mature B lymphocytes are necessary for acute splenic infection by γHV-68. Despite the lack of measurable acute infection, MuMT spleen cells harbored latent virus 6 weeks postinfection at a level about 100-fold higher than that in normal mice. These data demonstrate establishment of latency by a herpesvirus in an organ in the absence of acute viral replication in that organ. In addition, they demonstrate that γHV-68 can establish latency in a cell type other than mature B lymphocytes.