
A bifunctional HSV-vectored therapeutic vaccine can effectively reactivate latent viral reservoirs and elicit robust antigen-specific immune responses, providing a promising strategy for achieving a functional cure for chronic viral infections like HIV/SIV.


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The persistence of latent viral reservoirs remains the major obstacle to eradicating human immunodeficiency virus (HIV). We herein reported that recombinant herpes simplex virus type I (HSV-1) with ICP34.5 deletion could more effectively reactivate HIV latency than its wild-type counterpart. Mechanistically, HSV-ΔICP34.5 promoted the phosphorylation of HSF1 by decreasing the recruitment of protein phosphatase 1 (PP1α), thus effectively binding to the HIV LTR to reactivate the latent reservoirs. In addition, HSV-ΔICP34.5 enhanced the phosphorylation of IKKα/β through the degradation of IκBα, leading to p65 accumulation in the nucleus to elicit NF-κB pathway-dependent reactivation of HIV latency. Then, we constructed the recombinant HSV-ΔICP34.5 expressing simian immunodeficiency virus (SIV) env, gag, or the fusion antigen sPD1-SIVgag as an HIV therapeutic vaccine, aiming to achieve a functional cure by simultaneously reactivating viral latency and eliciting antigen-specific immune responses. Results showed that these constructs effectively elicited SIV-specific immune responses, reactivated SIV latency, and delayed viral rebound after the interruption of antiretroviral therapy (ART) in chronically SIV-infected rhesus macaques. Collectively, these findings provide insights into the rational design of HSV-vectored therapeutic strategies for pursuing an HIV functional cure.

### Competing Interest Statement

The authors have declared no competing interest.

Purging viral latency by a bifunctional HSV-vectored therapeutic vaccine in chronically SIV-infected macaques

efficient-reactivation-of-latent-viral-reservoirs-and-induction-of-antigen-specific-immune-responses-using-a-bifunctional-hsv-vectored-therapeutic-vaccine-in-chronically-siv-infected-macaques


Efficient Reactivation of Latent Viral Reservoirs and Induction of Antigen-Specific Immune Responses Using a Bifunctional HSV-Vectored Therapeutic Vaccine in Chronically SIV-Infected Macaques
