Restriction by SAMHD1 limits cGAS/STING-dependent innate and adaptive immune responses to HIV-1
SAMHD1 is a restriction factor for HIV-1 infection. . SAMHD1 mutations cause the autoinflammatory Aicardi-Goutières syndrome that is characterized by chronic type I interferon (IFN) secretion. We show that the spontaneous IFN response in SAMHD1-deficient cells and mice requires the cGAS/STING cytoso...
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| Fformat: | Journal article |
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Cell Press
2016
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| _version_ | 1826261284694261760 |
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| author | Maelfait, J Bridgeman, A Benlahrech, A Cursi, C Rehwinkel, J |
| author_facet | Maelfait, J Bridgeman, A Benlahrech, A Cursi, C Rehwinkel, J |
| author_sort | Maelfait, J |
| collection | OXFORD |
| description | SAMHD1 is a restriction factor for HIV-1 infection. . SAMHD1 mutations cause the autoinflammatory Aicardi-Goutières syndrome that is characterized by chronic type I interferon (IFN) secretion. We show that the spontaneous IFN response in SAMHD1-deficient cells and mice requires the cGAS/STING cytosolic DNA-sensing pathway. We provide genetic evidence that cell-autonomous control of lentivirus infection in myeloid cells by SAMHD1 limits virus-induced production of IFNs and the induction of co-stimulatory markers. This program of myeloid cell activation required reverse transcription, cGAS and STING, and signaling through the IFN receptor. Furthermore, SAMHD1 reduced the induction of virus-specific cytotoxic T cells in vivo. Therefore, virus restriction by SAMHD1 limits the magnitude of IFN and T cell responses. This demonstrates a competition between cell-autonomous virus control and subsequent innate and adaptive immune responses, a concept with important implications for the treatment of infection. Restriction factors defend infected cells against viruses. Maelfait et al. find that SAMHD1, which blocks HIV-1 infection in myeloid cells, prevents innate sensing of infection via cGAS/STING. Furthermore, SAMHD1 curtails virus-specific T cell responses in vivo. Restriction by SAMHD1, therefore, limits subsequent innate and adaptive immune responses. |
| first_indexed | 2024-03-06T19:19:02Z |
| format | Journal article |
| id | oxford-uuid:19692f86-c2ae-4333-9e97-abca5de7bf62 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T19:19:02Z |
| publishDate | 2016 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:19692f86-c2ae-4333-9e97-abca5de7bf622022-03-26T10:48:55ZRestriction by SAMHD1 limits cGAS/STING-dependent innate and adaptive immune responses to HIV-1Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:19692f86-c2ae-4333-9e97-abca5de7bf62Symplectic Elements at OxfordCell Press2016Maelfait, JBridgeman, ABenlahrech, ACursi, CRehwinkel, JSAMHD1 is a restriction factor for HIV-1 infection. . SAMHD1 mutations cause the autoinflammatory Aicardi-Goutières syndrome that is characterized by chronic type I interferon (IFN) secretion. We show that the spontaneous IFN response in SAMHD1-deficient cells and mice requires the cGAS/STING cytosolic DNA-sensing pathway. We provide genetic evidence that cell-autonomous control of lentivirus infection in myeloid cells by SAMHD1 limits virus-induced production of IFNs and the induction of co-stimulatory markers. This program of myeloid cell activation required reverse transcription, cGAS and STING, and signaling through the IFN receptor. Furthermore, SAMHD1 reduced the induction of virus-specific cytotoxic T cells in vivo. Therefore, virus restriction by SAMHD1 limits the magnitude of IFN and T cell responses. This demonstrates a competition between cell-autonomous virus control and subsequent innate and adaptive immune responses, a concept with important implications for the treatment of infection. Restriction factors defend infected cells against viruses. Maelfait et al. find that SAMHD1, which blocks HIV-1 infection in myeloid cells, prevents innate sensing of infection via cGAS/STING. Furthermore, SAMHD1 curtails virus-specific T cell responses in vivo. Restriction by SAMHD1, therefore, limits subsequent innate and adaptive immune responses. |
| spellingShingle | Maelfait, J Bridgeman, A Benlahrech, A Cursi, C Rehwinkel, J Restriction by SAMHD1 limits cGAS/STING-dependent innate and adaptive immune responses to HIV-1 |
| title | Restriction by SAMHD1 limits cGAS/STING-dependent innate and adaptive immune responses to HIV-1 |
| title_full | Restriction by SAMHD1 limits cGAS/STING-dependent innate and adaptive immune responses to HIV-1 |
| title_fullStr | Restriction by SAMHD1 limits cGAS/STING-dependent innate and adaptive immune responses to HIV-1 |
| title_full_unstemmed | Restriction by SAMHD1 limits cGAS/STING-dependent innate and adaptive immune responses to HIV-1 |
| title_short | Restriction by SAMHD1 limits cGAS/STING-dependent innate and adaptive immune responses to HIV-1 |
| title_sort | restriction by samhd1 limits cgas sting dependent innate and adaptive immune responses to hiv 1 |
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