LUNG EPITHELIAL-CELLS ARE A MAJOR SITE OF MURINE GAMMAHERPESVIRUS PERSISTENCE

It is currently believed that latently infected, resting B lymphocytes are central to gammaherpesvirus persistence, whereas mucosal epitheli al cells are considered nonessential. We have readdressed the question of nonlymphoid persistence using murine gammaherpesvirus 68 (MHV-68). To dissect lymphoid from nonlymphoid persistence, we used mu MT trans genic mice that are defective in B cells. MHV-68 DNA persisted in the lungs of intact and B cell-deficient mice. Both episomal and linear fo rms of the virus genome were present in lungs, implying the presence o f both latency and productive replication. In situ hybridization for v irus tRNA transcripts revealed latent MHV-68 in pulmonary epithelial c ells. Infectious virus was recovered from the lungs of mu MT mice afte r T cell depletion, showing that the persisting virus DNA was reactiva table. Finally, using adoptive transfer of B cells into B cell-deficie nt mice, it was shown that virus persisting in lungs seeded splenic B cells, and virus resident in the spleen seeded the lungs. These result s show that mucosal epithelia can act as a nonlymphoid reservoir for g ammaherpesvirus persistence, and that there is a two-way movement of v irus between lymphoid and nonlymphoid compartments during persistence.