Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4⁺ T cells.

ABSTRACT: Type I interferon (IFN) upregulates proteins that inhibit HIV within infected cells. Prior studies have identified IFN-stimulated genes (ISGs) that impede lab-adapted HIV in cell lines, yet the ISG(s) that mediate IFN restriction in HIV target cells, primary CD4⁺ T cells, are unknown. Here, we interrogate ISG restriction of primary HIV in CD4⁺ T cells by performing CRISPR-knockout screens with a custom library that specifically targets ISGs expressed in CD4⁺ T cells. Our investigation identifies previously undescribed HIV-restricting ISGs (HM13, IGFBP2, LAP3) and finds that two factors characterized in other HIV infection models (IFI16 and UBE2L6) mediate IFN restriction in T cells. Inactivation of these five ISGs in combination further diminishes IFN's pro

SUBMITTER: Itell HL 

PROVIDER: S-EPMC10592456 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature