Cyclic GMP-AMP Synthase Is an Innate Immune Sensor of HIV and Other Retroviruses

被引：855

作者：

Gao, Daxing ^{[1
]}

Wu, Jiaxi ^{[1
]}

Wu, You-Tong ^{[1
]}

Du, Fenghe ^{[1
,2
]}

Aroh, Chukwuemika ^{[3
,4
]}

Yan, Nan ^{[3
,4
]}

Sun, Lijun ^{[1
,2
]}

Chen, Zhijian J. ^{[1
,2
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA

[3] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA

[4] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA

来源：

SCIENCE | 2013年 / 341卷 / 6148期

关键词：

DNA SENSOR; 2ND-MESSENGER; DINUCLEOTIDE;

D O I：

10.1126/science.1240933

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Retroviruses, including HIV, can activate innate immune responses, but the host sensors for retroviruses are largely unknown. Here we show that HIV infection activates cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) to produce cGAMP, which binds to and activates the adaptor protein STING to induce type I interferons and other cytokines. Inhibitors of HIV reverse transcriptase, but not integrase, abrogated interferon-beta induction by the virus, suggesting that the reverse-transcribed HIV DNA triggers the innate immune response. Knockout or knockdown of cGAS in mouse or human cell lines blocked cytokine induction by HIV, murine leukemia virus, and simian immunodeficiency virus. These results indicate that cGAS is an innate immune sensor of HIV and other retroviruses.

引用

页码：903 / 906

页数：4

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