Murine gammaherpesvirus 68 genes both induce and suppress lymphoproliferative disease.

Gammaherpesvirus infection is associated with an increased incidence of lymphoproliferative disease in immunocompromised hosts. Murine gammaherpesvirus 68 (gammaHV68) infection of BALB beta(2)-microglobulin-deficient (BALB beta(2)m(-/-)) mice provides an animal model for analysis of the mechanisms responsible for the induction of a lymphoproliferative disease, atypical lymphoid hyperplasia (ALH), that is pathologically similar to posttransplant lymphoproliferative disease associated with Epstein-Barr virus infection. Here we report that the gammaHV68 v-cyclin and v-bcl-2 genes are required for the efficient induction of gammaHV68-associated ALH in BALB beta(2)m(-/-) mice, while the v-GPCR gene is dispensable for ALH induction. In contrast to these findings, deletion of the viral M1 gene enhanced ALH. Thus, gammaHV68 genes can either inhibit or enhance the induction of lymphoproliferative disease in immunocompromised mice.