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Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses.

ABSTRACT: 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-? 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.

SUBMITTER: Gao D

PROVIDER: S-EPMC3860819 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses.

Gao Daxing D Wu Jiaxi J Wu You-Tong YT Du Fenghe F Aroh Chukwuemika C Yan Nan N Sun Lijun L Chen Zhijian J ZJ

Science (New York, N.Y.) 20130808 6148

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-β induction by the virus, suggesting that the rev ...[more]

PMID: 23929945

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