The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1 (Nat Immunol, 2010, 11:1005-1013)

報告日期: 2011/03/08
報告時間: 13:10/16:00
報告學生: 陳逸純
講評老師: 王憲威
附件下載:

Full text: http://basicmed.med.ncku.edu.tw/admin/up_img/000308-3.pdf

The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1
Nan Yan, et al. 2010. Nature Immunology.11, 1005 - 1013
 
Speaker: Yi Chun Chen (陳逸純)
Commentator: Dr.Shainn-Wei Wang (王憲威老師)
Time: 15:10~16:00, Mar 08, 2011
Place: Room 602
 
Abstract:
Type I interferon is a crucial component of antiviral defense. Strikingly, infection of T cells and macrophages with human immunodeficiency virus type 1 (HIV-1) does not induce antiviral interferon responses. The authors found that the host cytoplasmic exonuclease TREX1 helps HIV evade innate immunity by digesting reverse transcripts that are not imported into the nucleus and would otherwise induce interferons. The interferon responses in TREX1-deficient cells after HIV-1 infection are inhibited by inhibitors of reverse transcriptase but not by inhibitors of integrase, which suggests that nonintegrated DNA is recognized by a DNA sensor. When TREX1 was inhibited by RNAi, HIV infection of primary cells triggered expression and secretion of type I interferon. The HIV-stimulated interferon response in cells deficient in TREX1, like the response to endogenous retroelement DNA and transfected DNA, was IRF3 dependent. They found that interferon induction in TREX1-deficient cells was blocked by the expression of enzymatically active TREX1 or by cosuppression of IRF3 expression to interrupt interferon signaling1. HIV-stimulated innate immune signaling also required STING and TBK1. On the basis of our siRNA experiments, they conclude that none of the known DNA sensors was involved. Therefore, their working model of the innate immune pathway activated by cytosolic HIV DNA starts with an unknown sensor that signals through STING, TBK1 and IRF3 to activate interferon expression.
 
References:
 
1.     Hornung, V. & Latz, E. 2010.Intracellular DNA recognition. Nat. Rev. Immunol. 10, 123–130.