Amazing stuff! We are still learning new things about the HIV virus! Beating viral pathogens one trick at a time!
"... According to the World Health Organization, at the end of 2021 more than 38 million people were living with HIV.
... a research team ... show for the first time that a protein, the aryl hydrocarbon receptor or AhR, plays a crucial role in this viral latency [hiding during antiretroviral therapy]. ...
To prove it, the scientists used the CRISPR/Cas9 system to knock out the expression of AhR. They also used drugs that induce or block AhR activation. With these two approaches neutralizing AhR activity, the team observed that viral growth occurred in CD4+ T cells of people living with HIV and on antiretroviral therapy. ..."
To prove it, the scientists used the CRISPR/Cas9 system to knock out the expression of AhR. They also used drugs that induce or block AhR activation. With these two approaches neutralizing AhR activity, the team observed that viral growth occurred in CD4+ T cells of people living with HIV and on antiretroviral therapy. ..."
From the highlights and abstract:
"Highlights
• AhR activation, induced upon TCR triggering, boosts non-pathogenic Th17 functions
• AhR gene editing decreases IL-22/IL-10 production and increases HIV-1 replication
• AhR pharmacological blockade promotes HIV outgrowth in cells of ART-treated PLWH
• AhR directly regulates HIC1, an HIV-1 repressor and tissue-residency regulator
Summary
The aryl hydrocarbon receptor (AhR) regulates Th17-polarized CD4+ T cell functions, but its role in HIV-1 replication/outgrowth remains unknown. Genetic (CRISPR-Cas9) and pharmacological inhibition reveal AhR as a barrier to HIV-1 replication in T cell receptor (TCR)-activated CD4+ T cells in vitro. In single-round vesicular stomatitis virus (VSV)-G-pseudotyped HIV-1 infection, AhR blockade increases the efficacy of early/late reverse transcription and subsequently facilitated integration/translation. Moreover, AhR blockade boosts viral outgrowth in CD4+ T cells of people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Finally, RNA sequencing reveals genes/pathways downregulated by AhR blockade in CD4+ T cells of ART-treated PLWH, including HIV-1 interactors and gut-homing molecules with AhR-responsive elements in their promoters. Among them, HIC1, a repressor of Tat-mediated HIV-1 transcription and a tissue-residency master regulator, is identified by chromatin immunoprecipitation as a direct AhR target. Thus, AhR governs a T cell transcriptional program controlling viral replication/outgrowth and tissue residency/recirculation, supporting the use of AhR inhibitors in “shock and kill” HIV-1 remission/cure strategies."
Identification of aryl hydrocarbon receptor as a barrier to HIV-1 infection and outgrowth in CD4+ T cells (open access)
Graphical abstract
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