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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Line
-
Gene Knockdown Techniques
-
HEK293 Cells
-
HIV / drug effects
-
HIV / enzymology
-
HIV / immunology*
-
HIV Infections / enzymology
-
HIV Infections / immunology*
-
HIV Infections / virology
-
HIV Reverse Transcriptase / antagonists & inhibitors
-
Humans
-
Immunity, Innate*
-
Interferon-beta / biosynthesis
-
Membrane Proteins / metabolism
-
Mice
-
Nucleotidyltransferases / genetics
-
Nucleotidyltransferases / metabolism*
-
Retroviridae / immunology
-
Retroviridae Infections / enzymology
-
Retroviridae Infections / immunology
-
Retroviridae Infections / virology
-
Reverse Transcriptase Inhibitors / pharmacology
Substances
-
Membrane Proteins
-
Reverse Transcriptase Inhibitors
-
STING1 protein, human
-
Sting1 protein, mouse
-
Interferon-beta
-
Nucleotidyltransferases
-
cGAS protein, human
-
cGAS protein, mouse
-
HIV Reverse Transcriptase