Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4+ T cells
Summary: 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,...
| मुख्य लेखकों: | , , |
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| स्वरूप: | लेख |
| भाषा: | English |
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Elsevier
2023-06-01
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| श्रृंखला: | Cell Reports |
| विषय: | |
| ऑनलाइन पहुंच: | http://www.sciencedirect.com/science/article/pii/S2211124723005673 |
| _version_ | 1827941647266086912 |
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| author | Hannah L. Itell Daryl Humes Julie Overbaugh |
| author_facet | Hannah L. Itell Daryl Humes Julie Overbaugh |
| author_sort | Hannah L. Itell |
| collection | DOAJ |
| description | Summary: 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 protective effect against 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. |
| first_indexed | 2024-03-13T09:42:50Z |
| format | Article |
| id | doaj.art-c22e4c12a18c4c768e94f1141b8e3c20 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-13T09:42:50Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-c22e4c12a18c4c768e94f1141b8e3c202023-05-25T04:24:17ZengElsevierCell Reports2211-12472023-06-01426112556Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4+ T cellsHannah L. Itell0Daryl Humes1Julie Overbaugh2Molecular and Cellular Biology PhD Program, University of Washington, Seattle, WA 98195, USA; Division of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA 98109, USADivision of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA 98109, USADivision of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA; Corresponding authorSummary: 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 protective effect against 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.http://www.sciencedirect.com/science/article/pii/S2211124723005673CP: Immunology |
| spellingShingle | Hannah L. Itell Daryl Humes Julie Overbaugh Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4+ T cells Cell Reports CP: Immunology |
| title | Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4+ T cells |
| title_full | Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4+ T cells |
| title_fullStr | Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4+ T cells |
| title_full_unstemmed | Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4+ T cells |
| title_short | Several cell-intrinsic effectors drive type I interferon-mediated restriction of HIV-1 in primary CD4+ T cells |
| title_sort | several cell intrinsic effectors drive type i interferon mediated restriction of hiv 1 in primary cd4 t cells |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723005673 |
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