In vitro induction of HIV-1 replication in resting CD4(+) T cells derived from individuals with undetectable plasma viremia upon stimulation with human T-cell leukemia virus type I.
Microbial coinfections have been associated with transient bursts of human immunodeficiency virus (HIV) viremia in patients. In this study we investigated whether human T-cell leukemia virus type I (HTLV-I), another human retrovirus that is prevalent among certain HIV-infected populations, can induce HIV-1 replication in patients who had been successfully treated with highly active antiretroviral therapy. We demonstrate that supernatants from HTLV-I-producing MT-2 cells can induce in vitro replication of HIV-1 from highly purified, resting CD4(+) T cells obtained from individuals with undetectable plasma viremia. Depletion of proinflammatory cytokines from the supernatants reduced, but did not abrogate, the ability to induce HIV-1 replication, indicating that other factors such as HTLV-I Tax or Env also have a role. The HTLV-I-mediated effect does not require productive infection: exposure to heat-inactivated HTLV-I virions, purified Tax protein, or HTLV-I Env glycoprotein also induced expression of HIV-1. Furthermore, we demonstrate that coculture of resting CD4(+) T cells with autologous CD8(+) T cells markedly inhibits the HTLV-I-induced virus replication. Our results suggest that coinfection with HTLV-I may induce viral replication in the latent viral reservoirs; however, CD8(+) T cells may play an important role in controlling the spread of virus upon microbial stimulation.
Moriuchi
H
H
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, 20892, USA. hiromori@net.nagasaki-u.ac.jp
Moriuchi
M
M
D019380:Anti-HIV Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D014779:Virus Replication
D019380:Anti-HIV Agents; D012367:RNA, Viral