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DNA sensor cGAS fends off viral infection

On today's Science Express, a paper by Xiao-Dong Li and Jiaxi Wu demonstrated that cGAS-cGAMP pathway plays pivotal roles in antiviral defense and immune adjuvant effects.

Summary: Invasion of microbial DNA into the cytoplasm of animal cells triggers a cascade of host immune reactions that help clear the infection; however, self DNA in the cytoplasm can cause autoimmune diseases. Biochemical approaches led to the identification of cyclic GMP-AMP (cGAMP) synthase (cGAS) as a cytosolic DNA sensor that triggers innate immune responses. Here, we show that cells from cGAS-deficient (cGas−/−) mice, including fibroblasts, macrophages and dendritic cells, failed to produce type I interferons and other cytokines in response to DNA transfection or DNA virus infection. cGas−/− mice were more susceptible to lethal infection with herpes simplex virus-1 (HSV1) than wild-type mice. We also show that cGAMP is an adjuvant that boosts antigen-specific T cell activation and antibody production in mice.

Pivotal Roles of cGAS-cGAMP Signaling in Antiviral Defense and Immune Adjuvant Effects.

Congratulations to Xiao-Dong, Jiaxi, Daxing, Hua, Josh and James!