This protein, known as STING (stimulator of interferon (IFN) genes), was identified in a screen of human proteins that could activate the IFNB promoter. Additional experiments showed that STING achieved this by inducing the activation of other factors that are central to triggering the innate antiviral response, such as IFN-regulatory factor 3 and nuclear factor-κB. In further support of a role for STING in mounting effective antiviral cellular responses, transfection of mouse embryonic fibroblasts with STING rendered them resistant to infection with vesicular stomatitis virus (VSV; a negative-stranded RNA virus), whereas the inhibition of STING expression in human embryonic kidney 293 cells markedly increased their susceptibility to VSV.
Comparison of STING-deficient and wild-type fibroblasts confirmed that STING is essential for optimal IFNβ production in response to VSV infection. However, STING was not required, at least in vitro, for IFNβ production in response to encephalomyocarditis virus, a positive-stranded RNA virus that is recognized through a pathway that is dependent on the intracellular sensor MDA5 (melanoma-differentiation-associated gene 5). Co-precipitation and microscopy analyses indicated that STING physically interacts with RIG-I (retinoic-acid-inducible gene I) but not MDA5, and that it acts downstream of RIG-I. So, STING seems to have an important downstream function in facilitating RIG-I-mediated detection of negative-stranded RNA viruses.
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