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

Daxing Gao, Jiaxi Wu, You Tong Wu, Fenghe Du, Chukwuemika Aroh, Nan Yan, Lijun Sun, Zhijian J. Chen

Research output: Contribution to journalArticle

426 Citations (Scopus)

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-β 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.

Original languageEnglish (US)
Pages (from-to)903-906
Number of pages4
JournalScience
Volume341
Issue number6148
DOIs
StatePublished - 2013

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GMP synthase (glutamine-hydrolyzing)
Retroviridae
HIV
Innate Immunity
Cytokines
HIV Reverse Transcriptase
Virus Activation
Integrases
Murine Leukemia Viruses
Simian Immunodeficiency Virus
Interferon Type I
Interferons
HIV Infections
Cell Line
cyclic guanosine monophosphate-adenosine monophosphate
DNA

ASJC Scopus subject areas

  • General

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Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses. / Gao, Daxing; Wu, Jiaxi; Wu, You Tong; Du, Fenghe; Aroh, Chukwuemika; Yan, Nan; Sun, Lijun; Chen, Zhijian J.

In: Science, Vol. 341, No. 6148, 2013, p. 903-906.

Research output: Contribution to journalArticle

Gao, Daxing ; Wu, Jiaxi ; Wu, You Tong ; Du, Fenghe ; Aroh, Chukwuemika ; Yan, Nan ; Sun, Lijun ; Chen, Zhijian J. / Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses. In: Science. 2013 ; Vol. 341, No. 6148. pp. 903-906.
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