Novis, Camille LArchin, Nancie MBuzon, Maria JVerdin, EricRound, June LLichterfeld, MathiasMargolis, David MPlanelles, VicenteBosque, Alberto2014-03-112013Novis, Camille L, Nancie M Archin, Maria J Buzon, Eric Verdin, June L Round, Mathias Lichterfeld, David M Margolis, Vicente Planelles, and Alberto Bosque. 2013. “Reactivation of latent HIV-1 in central memory CD4+ T cells through TLR-1/2 stimulation.” Retrovirology 10 (1): 119. doi:10.1186/1742-4690-10-119. http://dx.doi.org/10.1186/1742-4690-10-119.1742-4690http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879087Background: Toll-like receptors (TLRs) are crucial for recognition of pathogen-associated molecular patterns by cells of the innate immune system. TLRs are present and functional in CD4+ T cells. Memory CD4+ T cells, predominantly central memory cells (TCM), constitute the main reservoir of latent HIV-1. However, how TLR ligands affect the quiescence of latent HIV within central memory CD4+ T cells has not been studied. Results: We evaluated the ability of a broad panel of TLR agonists to reactivate latent HIV-1. The TLR-1/2 agonist Pam3CSK4 leads to viral reactivation of quiescent HIV in a model of latency based on cultured TCM and in resting CD4+ T cells isolated from aviremic patients. In addition, we investigated the signaling pathway associated with Pam3CSK4 involved in HIV-1 reactivation. We show that the transcription factors NFκB, NFAT and AP-1 cooperate to induce viral reactivation downstream of TLR-1/2 stimulation. Furthermore, increasing levels of cyclin T1 is not required for TLR-mediated viral reactivation, but induction of viral expression requires activated pTEFb. Finally, Pam3CSK4 reactivates latent HIV-1 in the absence of T cell activation or proliferation, in contrast to antigen stimulation. Conclusions: Our findings suggest that the signaling through TLR-1/2 pathway via Pam3CSK4 or other reagents should be explored as an anti-latency strategy either alone or in combination with other anti-latency drugs.en-USJournal Article2014-03-1110.1186/1742-4690-10-119