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The cytosolic exonuclease TREX1 inhibits the innate immune response to HIV-1
Viral infection triggers innate immune sensors to produce type I interferons (IFN). However, HIV infection of T cells and macrophages does not trip these alarms. How HIV avoids activating nucleic acid sensors is unknown. The cytosolic exonuclease TREX1 suppressed IFN triggered by HIV. In Trex1(−/−)...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
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2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958248/ https://www.ncbi.nlm.nih.gov/pubmed/20871604 http://dx.doi.org/10.1038/ni.1941 |
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author | Yan, Nan Regalado-Magdos, Ashton D. Stiggelbout, Bart Lee-Kirsch, Min Ae Lieberman, Judy |
author_facet | Yan, Nan Regalado-Magdos, Ashton D. Stiggelbout, Bart Lee-Kirsch, Min Ae Lieberman, Judy |
author_sort | Yan, Nan |
collection | PubMed |
description | Viral infection triggers innate immune sensors to produce type I interferons (IFN). However, HIV infection of T cells and macrophages does not trip these alarms. How HIV avoids activating nucleic acid sensors is unknown. The cytosolic exonuclease TREX1 suppressed IFN triggered by HIV. In Trex1(−/−) mouse cells and human CD4(+) T cells and macrophages in which TREX1 was inhibited by RNA interference, cytosolic HIV DNA accumulated, and HIV infection induced type I IFN that inhibited HIV replication and spreading. TREX1 bound to cytosolic HIV DNA and digested excess HIV DNA that would otherwise activate IFN expression via a TBK1, STING and IRF3 dependent pathway. HIV-stimulated IFN production in cells deficient in TREX1 did not involve known nucleic acid sensors. |
format | Text |
id | pubmed-2958248 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
record_format | MEDLINE/PubMed |
spelling | pubmed-29582482011-05-01 The cytosolic exonuclease TREX1 inhibits the innate immune response to HIV-1 Yan, Nan Regalado-Magdos, Ashton D. Stiggelbout, Bart Lee-Kirsch, Min Ae Lieberman, Judy Nat Immunol Article Viral infection triggers innate immune sensors to produce type I interferons (IFN). However, HIV infection of T cells and macrophages does not trip these alarms. How HIV avoids activating nucleic acid sensors is unknown. The cytosolic exonuclease TREX1 suppressed IFN triggered by HIV. In Trex1(−/−) mouse cells and human CD4(+) T cells and macrophages in which TREX1 was inhibited by RNA interference, cytosolic HIV DNA accumulated, and HIV infection induced type I IFN that inhibited HIV replication and spreading. TREX1 bound to cytosolic HIV DNA and digested excess HIV DNA that would otherwise activate IFN expression via a TBK1, STING and IRF3 dependent pathway. HIV-stimulated IFN production in cells deficient in TREX1 did not involve known nucleic acid sensors. 2010-09-26 2010-11 /pmc/articles/PMC2958248/ /pubmed/20871604 http://dx.doi.org/10.1038/ni.1941 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Yan, Nan Regalado-Magdos, Ashton D. Stiggelbout, Bart Lee-Kirsch, Min Ae Lieberman, Judy The cytosolic exonuclease TREX1 inhibits the innate immune response to HIV-1 |
title | The cytosolic exonuclease TREX1 inhibits the innate immune response to HIV-1 |
title_full | The cytosolic exonuclease TREX1 inhibits the innate immune response to HIV-1 |
title_fullStr | The cytosolic exonuclease TREX1 inhibits the innate immune response to HIV-1 |
title_full_unstemmed | The cytosolic exonuclease TREX1 inhibits the innate immune response to HIV-1 |
title_short | The cytosolic exonuclease TREX1 inhibits the innate immune response to HIV-1 |
title_sort | cytosolic exonuclease trex1 inhibits the innate immune response to hiv-1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958248/ https://www.ncbi.nlm.nih.gov/pubmed/20871604 http://dx.doi.org/10.1038/ni.1941 |
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