Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4 + T cells.
bioRxiv
; 2023 Feb 07.
Article
em En
| MEDLINE
| ID: mdl-36798236
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. We performed CRISPR-knockout screens using a custom library that specifically targets ISGs expressed in CD4 + T cells and validated top hits. Our investigation identified new HIV-restricting ISGs (HM13, IGFBP2, LAP3) and found that two previously studied factors (IFI16, UBE2L6) are IFN effectors in T cells. Inactivation of these five ISGs in combination further diminished IFNâ™s protective effect against six diverse HIV strains. This work demonstrates that IFN restriction of HIV is multifaceted, resulting from several effectors functioning collectively, and establishes a primary cell ISG screening model to identify both single and combinations of HIV-restricting ISGs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article