PATHOGENESIS OF MURINE GAMMAHERPESVIRUS INFECTION IN MICE DEFICIENT IN CD4 AND CD8 T-CELLS

Murine gammaherpesvirus is a natural pathogen of wild mice. The virus infects alveolar cells and spleen cells during the primary infection a nd establishes a latent/persistent infection in B lymphocytes. Little is known about the immunological response to gammaherpesviruses during a primary infection. To address this issue, we investigated the patho genesis of murine herpesvirus 68 (MHV-68) infection in mice deficient in CD4 or CD8 T-cell populations. Infection of the lung and spleen wer e greatly exacerbated in CD8-deficient mice, reflected by elevated vir us titers in the lung and an increase in the number of infected spleno cytes located around germinal centers. This finding contrasts with cle arance of virus from the lung and spleen by day 12 postinfection in CD 4-depleted animals. These data clearly indicate a major role for CD8 T cells in recovery from an acute MHV-68 infection. Whereas CD4 T cells fail to influence the course of infection in the lung, they do contri bute to lymphoproliferation seen in the spleen (splenomegaly) during t he primary infection. The significance of these results are discussed in relation to the immune response to other herpesviruses, in particul ar Epstein-Barr virus, with which MHV-68 shares similar molecular and biological properties.