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...

Ful tanımlama

Detaylı Bibliyografya
Asıl Yazarlar: Maelfait, J, Bridgeman, A, Benlahrech, A, Cursi, C, Rehwinkel, J
Materyal Türü: Journal article
Baskı/Yayın Bilgisi: Cell Press 2016
_version_ 1826261284694261760
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
work_keys_str_mv AT maelfaitj restrictionbysamhd1limitscgasstingdependentinnateandadaptiveimmuneresponsestohiv1
AT bridgemana restrictionbysamhd1limitscgasstingdependentinnateandadaptiveimmuneresponsestohiv1
AT benlahrecha restrictionbysamhd1limitscgasstingdependentinnateandadaptiveimmuneresponsestohiv1
AT cursic restrictionbysamhd1limitscgasstingdependentinnateandadaptiveimmuneresponsestohiv1
AT rehwinkelj restrictionbysamhd1limitscgasstingdependentinnateandadaptiveimmuneresponsestohiv1