Gladstone Institutes and UCSF reported a genome-wide CRISPR map of human genes that either promote or restrict HIV infection in primary CD4+ T cells. Published in Cell, the study addresses a longstanding limitation of HIV work in immortalized cell lines by using primary cells more representative of the immune target in vivo. Researchers optimized conditions to raise HIV infection rates to about 70% in culture, enabling orthogonal genome-wide CRISPR activation (CRISPRa) and CRISPR knockout (CRISPRn) screens. Disrupting genes identified factors HIV depends on, while over-activating genes revealed antiviral defenses that HIV suppresses. The team said the resulting genetic blueprint clarifies host–virus interactions at scale and could inform future target discovery for immune-based HIV interventions.