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

Abstract

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.