Juan Lama: New HIV Cure Approach Forces Hidden Virus into Tripping Immune Sensor
Juan Lama, Founder and Chief Scientific Officer at RetroVirox Inc., shared a post on LinkedIn:
“New HIV Cure Approach Forces Hidden Virus into Tripping Immune Sensor
The brief News article comments on the new HIV cure approach recently presented at the Conference on Retroviruses and Other Opportunistic Infections (CROI).
The strategy relies on one of the many internal sensors T cells and macrophages use to detect microbes, CARD8 (Caspase Recruitment Domain-containing protein 8).
CARD8 detects key viral enzymes called proteases, and it triggers an inflammatory form of cell death known as pyropptosis that avoids the production of infectious particles.
In HIV expressing cells CARD8 detects dimers of the HIV viral protease.
The viral protease dimerizes only when the new viral particles are exiting the host cell, and by delaying the process the virus avoids recognition of producer cells by CARD8.
A team at Washington University in St. Louis found that treatment with efavirenz and rilpivirine, inhibitors of the HIV reverse transcriptase, somehow trigger the premature dimerization of protease inside infected cells and reinstate the innate immune response mediated by CARD8 in HIV producer cells, leading to pyroptosis.
Researchers validated the use of efavirenz in HIV infected patients by showing that when the inhibitor is added to the regime of a cohort of infected people that were successfully controlling the virus, the HIV latent reservoir is significantly reduced in 4 months (20% to 50%) in the majority (6 of 7) of the participants.
Merck reported in 2023 the development of a novel reverse transcriptase inhibitor that is an order of magnitude more potent than efavirenz at dimerizing the viral protease in vitro.
It is expected that it will be tested in the future for its efficacy in reducing the latently infected viral reservoir.
The findings highlight the possibility of creating new combinations of antiretrovirals including dimerizers of the HIV protease that might facilitate reduction of viral reservoir pool in the presence of latency reversal agents.”
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