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.
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-kappaB 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.
Thibault
Sandra
S
Centre de Recherche en Infectiologie, Centre Hospitalier de l'Université Laval; Faculté de Médecine, Université Laval, Québec G1V4G2, Canada.
Imbeault
Michaël
M
Tardif
Mélanie R
MR
Tremblay
Michel J
MJ
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D005408:Flagellin / Q000276:immunology; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D007156:Immunologic Memory; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation; D016328:NF-kappa B / Q000276:immunology; D011533:Proviruses / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000276:immunology* / Q000378:metabolism; D014775:Virus Activation / Q000276:immunology*; D017735:Virus Latency
D016328:NF-kappa B; D012333:RNA, Messenger; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; D005408:Flagellin