STINGing CD4+ T cells to induce refractoriness to HIV infection

Abstract HIV rapidly infects CD4+ T cells where it can establish latent infection. Identifying immune mechanisms which render refractory to infection represents a critical step in limiting and viral spread. Using purified memory from healthy donors, we found that activation of the STING signaling pathway with 0.5 mM agonist diABZI was sufficient induce state refractoriness vitro cells, major source reservoir. We observed induces Type I IFN production activates p-IRF3. CRISPR KD led significant increase infection, demonstrating cell intrinsic role for infection/replication. proteomics, identified significantly potently restriction factors proteins involved antiviral immunity 1 signaling. Importantly, were reduced mapped pathways including RNA processing protein translation are aspects host machinery needs co-opt replicate produce infectious virions. Our data provide mechanistic insight into as means highlights this lands “1–2” punch by increasing expression directly target virus while suppressing cellular needed life cycle. The potential use post-exposure therapeutic limits promoting global novel strategy may stop its tracks.