CRITICAL ROLE FOR CD4(-CELLS IN CONTROLLING RETROVIRUS REPLICATION AND SPREAD IN PERSISTENTLY INFECTED MICE() T)

Reactivations of persistent viral infections pose a significant medica l problem in immunocompromised cancer, transplant, and AIDS patients, yet little is known about how persistent viral infections are immunolo gically controlled. Here we describe a mouse model for investigating t he role of the immune response in controlling a persistent retroviral infection. We demonstrate that, following recovery from acute Friend v irus infection, a small number of B cells evade immunological destruct ion and harbor persistent virus. In vivo depletions of T-cell subsets in persistently infected mice revealed a critical role for CD4(+) T ce lls in controlling virus replication,spread to the erythroid lineage, and induction of erythroleukemia, The CD4(+) T-cell effect was indepen dent of CD8(+) T cells and in some cases was also independent of virus -neutralizing antibody responses. Thus, the CD4(+) T cells may have ha d a direct antiviral effect. These results may have relevance for huma n immunodeficiency virus (HIV) infections where loss of CD4(+) T cells is associated,vith an increase in HIV replication, reactivation of pe rsistent viruses, and a high incidence of virus-associated cancers.