DC CFAR investigators, Alberto Bosque, PhD, and Amanda Macedo, PhD, along with their colleagues, have published an article in JCI Insight entitled, "Dual TLR2 and TLR7 agonists as HIV latency-reversing agents".
This article discusses a study that looked at synthetic molecules composed of dual TLR2 and TLR7 agonists as latency reversing agents, comparing their activity with that of the TLR2 agonist Pam2CSK4 and the TLR7 agonist GS-9620. This approach was utilized to further investigate latency-reversing agents that could prompt viral reactivation and lead to immune cell recognition and elimination of latently infected cells - known as the shock-and-kill strategy. The authors found that the dual TLR2/7 agonists reactivated latency through two complementary mechanisms. The TLR2 component reactivated HIV by inducing NF-κB activation in memory CD4+ T cells, while the TLR7 component induced the secretion of TNF-α by monocytes and plasmacytoid dendritic cells, promoting viral reactivation in CD4+ T cells. Further, the TLR2 component induced the secretion of IL-22, which promoted an antiviral state, blocking HIV infection in CD4+ T cells. The authors hope this study will provide insight into the use of these agonists as a comprehensive approach to targeting the eradication of latent HIV.
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