Regulation of STING activity in DNA sensing by ISG15 modification

Sensing of human immunodeficiency virus type 1 (HIV-1) DNA is mediated by the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling axis. Signal transduction and regulation of this cascade is achieved by post-translational modifications. Here we show that cGAS-STING-dependent HIV-1 sensing requires interferon-stimulated gene 15 (ISG15). ISG15 deficiency inhibits STING-dependent sensing of HIV-1 and STING agonist-induced antiviral response. Upon external stimuli, STING undergoes ISGylation at residues K224, K236, K289, K347, K338, and K370. Inhibition of STING ISGylation at K289 suppresses STING-mediated type

• Lin, C.
• Kuffour, E. O.
• Fuchs, N. V.
• Gertzen, C. G. W.
• Kaiser, J.
• Hirschenberger, M.
• Tang, X.
• Xu, H. C.
• Michel, O.
• Tao, R.
• Haase, A.
• Martin, U.
• Kurz, T.
• Drexler, I.
• Görg, B.
• Lang, P. A.
• Luedde, T.
• Sparrer, K. M. J.
• Gohlke, H.
• König, R.
• Münk, C.