TY - JOUR
T1 - Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses
AU - Gao, Daxing
AU - Wu, Jiaxi
AU - Wu, You Tong
AU - Du, Fenghe
AU - Aroh, Chukwuemika
AU - Yan, Nan
AU - Sun, Lijun
AU - Chen, Zhijian J.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1240933
DO - 10.1126/science.1240933
M3 - Article
C2 - 23929945
AN - SCOPUS:84882896267
SN - 0036-8075
VL - 341
SP - 903
EP - 906
JO - Science
JF - Science
IS - 6148
ER -