Gladstone Institutes and UCSF published a genome-wide CRISPR map of host factors that either promote or restrict HIV infection in primary human CD4+ T cells. Published in Cell, the work addresses the gap between earlier studies in immortalized lines and the biology of the cells HIV actually infects in vivo. The team reported that years of optimization improved infection rates from ~1–2% to roughly 70%, enabling orthogonal genome-wide CRISPR activation (CRISPRa) and knockout (CRISPRn) screens. The screens tested nearly every human gene to reveal both viral dependencies and antiviral defenses. Lead author Ujjwal Rathore and senior author Alex Marson described the resulting “blueprint” of the host–virus interface, including genes previously unknown to influence infection outcomes in primary T cells. The dataset is expected to feed target prioritization for antiviral and immune-modulating strategies. —