The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1
Open Access
- 26 September 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Immunology
- Vol. 11 (11), 1005-1013
- https://doi.org/10.1038/ni.1941
Abstract
Cells infected with human immunodeficiency virus type 1 do not produce type I interferon responses. Lieberman and colleagues report that the cytosolic exonuclease TREX1 prevents the accumulation of replication intermediates of this virus that could otherwise trigger intracellular sensors. Viral infection triggers innate immune sensors to produce type I interferon. However, infection of T cells and macrophages with human immunodeficiency virus (HIV) does not trip those alarms. How HIV avoids activating nucleic acid sensors is unknown. Here we found that the cytosolic exonuclease TREX1 suppressed interferon triggered by HIV. In Trex1−/− mouse cells and human CD4+ T cells and macrophages in which TREX1 was inhibited by RNA-mediated interference, cytosolic HIV DNA accumulated and HIV infection induced type I interferon that inhibited HIV replication and spreading. TREX1 bound to cytosolic HIV DNA and digested excess HIV DNA that would otherwise activate interferon expression via a pathway dependent on the kinase TBK1, the adaptor STING and the transcription factor IRF3. HIV-stimulated interferon production in cells deficient in TREX1 did not involve known nucleic acid sensors.Keywords
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