Critical role for CD4(+) T cells in controlling retrovirus replication and spread in persistently infected mice.
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.
Hasenkrug
K J
KJ
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA. KHasenkrug@nih.gov
Brooks
D M
DM
Dittmer
U
U
D000818:Animals; D001402:B-Lymphocytes / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005622:Friend murine leukemia virus / Q000276:immunology* / Q000502:physiology; D004915:Leukemia, Erythroblastic, Acute; D007942:Leukemia, Experimental / Q000276:immunology* / Q000821:virology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012192:Retroviridae Infections / Q000276:immunology* / Q000821:virology; D013163:Splenomegaly; D014412:Tumor Virus Infections / Q000276:immunology* / Q000821:virology; D017735:Virus Latency; D014779:Virus Replication