The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1

Nan Yan, Ashton D. Regalado-Magdos, Bart Stiggelbout, Min Ae Lee-Kirsch, Judy Lieberman

Research output: Contribution to journalArticle

324 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1005-1013
Number of pages9
JournalNature Immunology
Volume11
Issue number11
DOIs
StatePublished - Nov 2010

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Exonucleases
Innate Immunity
HIV-1
HIV
Interferons
Interferon Type I
Virus Diseases
Nucleic Acids
DNA
Macrophages
T-Lymphocytes
Virus Replication
RNA Interference
Transcription Factors
Phosphotransferases

ASJC Scopus subject areas

  • Immunology

Cite this

Yan, N., Regalado-Magdos, A. D., Stiggelbout, B., Lee-Kirsch, M. A., & Lieberman, J. (2010). The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1. Nature Immunology, 11(11), 1005-1013. https://doi.org/10.1038/ni.1941

The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1. / Yan, Nan; Regalado-Magdos, Ashton D.; Stiggelbout, Bart; Lee-Kirsch, Min Ae; Lieberman, Judy.

In: Nature Immunology, Vol. 11, No. 11, 11.2010, p. 1005-1013.

Research output: Contribution to journalArticle

Yan, N, Regalado-Magdos, AD, Stiggelbout, B, Lee-Kirsch, MA & Lieberman, J 2010, 'The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1', Nature Immunology, vol. 11, no. 11, pp. 1005-1013. https://doi.org/10.1038/ni.1941
Yan, Nan ; Regalado-Magdos, Ashton D. ; Stiggelbout, Bart ; Lee-Kirsch, Min Ae ; Lieberman, Judy. / The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1. In: Nature Immunology. 2010 ; Vol. 11, No. 11. pp. 1005-1013.
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