This manuscript is accompanied by a News and Views in Nature Immunology. Many thanks to Drs. Melanie Ott and Zichong Li @TheOttLabfor authoring it. Here is the link: nature.com/articles/s4159

This work was a collaboration between Valadkhan lab and Dr. Jonathan Karn's lab, with @LeahPlasek
and @persilon doing most of the experimental heavylifting, and funded by @NIDAnews and @NIAIDNews. Link to the manuscript: bit.ly/4nwyEQQ

So, formation of the latent HIV reservoir, the main barrier to #HIVcure, isn't a random process, but a deliberate survival strategy by HIV. This work has major implications for #EndHIV efforts by uncovering new therapeutic targets to address critical gaps in existing therapies.

We showed that post-integration expression of viral genes activates two key anti-proliferative pathways, p53 and KLF2, leading to strong MYC suppression, cellular quiescence, and notably, proviral latency in a subset of infected cells. We confirmed key results in cells from PWH.

We studied global gene expression patterns in CD4+ T cells at early time points after HIV infection. We also, for the first time, defined the mechanism of quiescence in CD4+ cells. The similarities were striking: HIV actively drives T cells into quiescence! How did this happen?