Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses.
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.
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Daxing
D
Gao
Jiaxi
J
Wu
You-Tong
YT
Wu
Fenghe
F
Du
Chukwuemika
C
Aroh
Nan
N
Yan
Lijun
L
Sun
Zhijian J
ZJ
Chen
D000818:Animals; D002460:Cell Line; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006678:HIV / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D015658:HIV Infections / Q000201:enzymology / Q000276:immunology* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D006801:Humans; D007113:Immunity, Innate; D016899:Interferon-beta / Q000096:biosynthesis; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009713:Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae / Q000276:immunology; D012192:Retroviridae Infections / Q000201:enzymology / Q000276:immunology / Q000821:virology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D000099197:STING Protein; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
D054303:HIV Reverse Transcriptase; D016899:Interferon-beta; D008565:Membrane Proteins; D009713:Nucleotidyltransferases; D018894:Reverse Transcriptase Inhibitors; C532857:STING1 protein, human; D000099197:STING Protein; C530855:Sting1 protein, mouse; C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase; C578391:cGAS protein, mouse