Abstract
Cyclic GMP-AMP synthase (cGAS) detects cytosolic DNA during virus infection and induces an antiviral state. cGAS signals by synthesis of a second messenger, cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING). We show that cGAMP is incorporated into viral particles, including lentivirus and herpesvirus virions, when these are produced in cGAS-expressing cells. Virions transferred cGAMP to newly infected cells and triggered a STING-dependent antiviral program. These effects were independent of exosomes and viral nucleic acids. Our results reveal a way by which a signal for innate immunity is transferred between cells, potentially accelerating and broadening antiviral responses. Moreover, infection of dendritic cells with cGAMP-loaded lentiviruses enhanced their activation. Loading viral vectors with cGAMP therefore holds promise for vaccine development.
Copyright © 2015, American Association for the Advancement of Science.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
AIDS Vaccines / immunology
-
Dendritic Cells / immunology
-
Dendritic Cells / virology
-
Genes, Reporter
-
Genetic Vectors / genetics
-
Genetic Vectors / metabolism
-
HEK293 Cells
-
HIV Infections / immunology*
-
HIV Infections / metabolism
-
HIV Infections / prevention & control
-
HIV-1 / genetics
-
HIV-1 / metabolism*
-
Herpes Simplex / immunology*
-
Herpes Simplex / prevention & control
-
Herpes Simplex Virus Vaccines / immunology
-
Herpesvirus 1, Human / genetics
-
Herpesvirus 1, Human / metabolism*
-
Humans
-
Immunity, Innate / genetics
-
Immunity, Innate / immunology
-
Interferon-beta / genetics
-
Interferon-beta / immunology*
-
Nucleotides, Cyclic / metabolism*
-
Promoter Regions, Genetic
-
Second Messenger Systems*
-
Transcriptional Activation
-
Virion / genetics
-
Virion / metabolism*
Substances
-
AIDS Vaccines
-
Herpes Simplex Virus Vaccines
-
Nucleotides, Cyclic
-
cyclic guanosine monophosphate-adenosine monophosphate
-
Interferon-beta