Critical Role for CD4 + T Cells in Controlling Retrovirus Replication and Spread in Persistently Infected Mice

Abstract

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