SAMHD1 restricts HIV-1 replication and regulates interferon production in mouse myeloid cells.
SAMHD1 restricts the replication of HIV-1 and other retroviruses in human myeloid and resting CD4(+) T cells and that is counteracted in SIV and HIV-2 by the Vpx accessory protein. The protein is a phosphohydrolase that lowers the concentration of deoxynucleoside triphosphates (dNTP), blocking rever...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089558&type=printable |
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| author | Ruonan Zhang Nicolin Bloch Laura A Nguyen Baek Kim Nathaniel R Landau |
| author_facet | Ruonan Zhang Nicolin Bloch Laura A Nguyen Baek Kim Nathaniel R Landau |
| author_sort | Ruonan Zhang |
| collection | DOAJ |
| description | SAMHD1 restricts the replication of HIV-1 and other retroviruses in human myeloid and resting CD4(+) T cells and that is counteracted in SIV and HIV-2 by the Vpx accessory protein. The protein is a phosphohydrolase that lowers the concentration of deoxynucleoside triphosphates (dNTP), blocking reverse transcription of the viral RNA genome. Polymorphisms in the gene encoding SAMHD1 are associated with Aicardi-Goutières Syndrome, a neurological disorder characterized by increased type-I interferon production. SAMHD1 is conserved in mammals but its role in restricting virus replication and controlling interferon production in non-primate species is not well understood. We show that SAMHD1 is catalytically active and expressed at high levels in mouse spleen, lymph nodes, thymus and lung. siRNA knock-down of SAMHD1 in bone marrow-derived macrophages increased their susceptibility to HIV-1 infection. shRNA knock-down of SAMHD1 in the murine monocytic cell-line RAW264.7 increased its susceptibility to HIV-1 and murine leukemia virus and increased the levels of the dNTP pool. In addition, SAMHD1 knock-down in RAW264.7 cells induced the production of type-I interferon and several interferon-stimulated genes, modeling the situation in Aicardi-Goutières Syndrome. Our findings suggest that the role of SAMHD1 in restricting viruses is conserved in the mouse. The RAW264.7 cell-line serves as a useful tool to study the antiviral and innate immune response functions of SAMHD1. |
| format | Article |
| id | doaj-art-9d1b9dfe10ea42ff909ab0337e5a8f78 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-9d1b9dfe10ea42ff909ab0337e5a8f782025-08-20T03:01:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0192e8955810.1371/journal.pone.0089558SAMHD1 restricts HIV-1 replication and regulates interferon production in mouse myeloid cells.Ruonan ZhangNicolin BlochLaura A NguyenBaek KimNathaniel R LandauSAMHD1 restricts the replication of HIV-1 and other retroviruses in human myeloid and resting CD4(+) T cells and that is counteracted in SIV and HIV-2 by the Vpx accessory protein. The protein is a phosphohydrolase that lowers the concentration of deoxynucleoside triphosphates (dNTP), blocking reverse transcription of the viral RNA genome. Polymorphisms in the gene encoding SAMHD1 are associated with Aicardi-Goutières Syndrome, a neurological disorder characterized by increased type-I interferon production. SAMHD1 is conserved in mammals but its role in restricting virus replication and controlling interferon production in non-primate species is not well understood. We show that SAMHD1 is catalytically active and expressed at high levels in mouse spleen, lymph nodes, thymus and lung. siRNA knock-down of SAMHD1 in bone marrow-derived macrophages increased their susceptibility to HIV-1 infection. shRNA knock-down of SAMHD1 in the murine monocytic cell-line RAW264.7 increased its susceptibility to HIV-1 and murine leukemia virus and increased the levels of the dNTP pool. In addition, SAMHD1 knock-down in RAW264.7 cells induced the production of type-I interferon and several interferon-stimulated genes, modeling the situation in Aicardi-Goutières Syndrome. Our findings suggest that the role of SAMHD1 in restricting viruses is conserved in the mouse. The RAW264.7 cell-line serves as a useful tool to study the antiviral and innate immune response functions of SAMHD1.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089558&type=printable |
| spellingShingle | Ruonan Zhang Nicolin Bloch Laura A Nguyen Baek Kim Nathaniel R Landau SAMHD1 restricts HIV-1 replication and regulates interferon production in mouse myeloid cells. PLoS ONE |
| title | SAMHD1 restricts HIV-1 replication and regulates interferon production in mouse myeloid cells. |
| title_full | SAMHD1 restricts HIV-1 replication and regulates interferon production in mouse myeloid cells. |
| title_fullStr | SAMHD1 restricts HIV-1 replication and regulates interferon production in mouse myeloid cells. |
| title_full_unstemmed | SAMHD1 restricts HIV-1 replication and regulates interferon production in mouse myeloid cells. |
| title_short | SAMHD1 restricts HIV-1 replication and regulates interferon production in mouse myeloid cells. |
| title_sort | samhd1 restricts hiv 1 replication and regulates interferon production in mouse myeloid cells |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0089558&type=printable |
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