Gladstone Institutes and UCSF reported a genome-wide CRISPR map of human genes that promote or restrict HIV infection in primary CD4+ T cells. Published in Cell, the work provides a host–virus blueprint derived from the cell type HIV naturally targets, addressing limitations of prior studies using immortalized cell lines. The team overcame low infection efficiency in primary cells by boosting HIV infection rates to roughly 70% after optimization, enabling both CRISPR activation (CRISPRa) and knockout (CRISPRn) screens across near-complete gene sets. Perturbations revealed dependencies HIV exploits and antiviral defenses the virus suppresses. Researchers said the dataset can guide target selection for future host-directed therapies and improve understanding of why infection outcomes vary between individuals and contexts.