TLR5 stimulation is sufficient to trigger reactivation of latent HIV-1 provirus in T lymphoid cells and activate virus gene expression in central memory CD4+ T cells

• Published in: Virology (New York, N.Y.) Vol. 389; no. 1; pp. 20 - 25
• Main Authors: Thibault, Sandra, Imbeault, Michaël, Tardif, Mélanie R, Tremblay, Michel J
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.06.2009
• Subjects: CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; Flagellin - immunology; Gene Expression Regulation, Viral; HIV Infections - immunology; HIV Infections - virology; HIV-1; HIV-1 - genetics; HIV-1 - immunology; HIV-1 - physiology; Humans; Immunologic Memory; Infectious Disease; Jurkat Cells; Latency; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - virology; Lymphocyte Activation; NF-kappa B - immunology; Proviruses - genetics; Proviruses - immunology; Proviruses - physiology; RNA, Messenger - metabolism; T cells; TLR; Toll-Like Receptor 5 - immunology; Toll-Like Receptor 5 - metabolism; Virus Activation - immunology; Virus Latency; HIV-1; TLR; T cells; Latency
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2009.04.019

Abstract When effector CD4+ T cells carrying integrated HIV-1 proviruses revert back to a resting memory state, the virus can remain silent in those cells for years. Following re-exposure to the nominal antigen or in response to other stimuli (e.g. pro-inflammatory cytokines), these cells can begin to produce virus. Here we demonstrate that TLR5 stimulation induces activation of NF-κB and reactivate latent HIV-1 in CD4+ T lymphoid cells. Interestingly, we report also that TLR5 engagement leads to virus gene expression in quiescent central memory CD4+ T cells, a cell population recognized as a major reservoir in infected individuals. This study supports the hypothesis that translocation of microbes that can engage pathogen recognition receptors might play a dominant role in chronic immune activation seen in HIV-1-infected individuals and promote virus replication and dissemination.