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Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang
Control Of Antiviral Innate Immune Response By Protein Geranylgeranylation, Shigao Yang, Zhaozhao Jiang, Katherine A. Fitzgerald, Donghai Wang
Katherine A. Fitzgerald
The mitochondrial antiviral signaling protein (MAVS) orchestrates host antiviral innate immune response to RNA virus infection. However, how MAVS signaling is controlled to eradicate virus while preventing self-destructive inflammation remains obscure. Here, we show that protein geranylgeranylation, a posttranslational lipid modification of proteins, limits MAVS-mediated immune signaling by targeting Rho family small guanosine triphosphatase Rac1 into the mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) at the mitochondria-ER junction. Protein geranylgeranylation and subsequent palmitoylation promote Rac1 translocation into MAMs upon viral infection. MAM-localized Rac1 limits MAVS' interaction with E3 ligase Trim31 and hence inhibits MAVS ubiquitination, aggregation, and activation. Rac1 also facilitates …
Sensing Of Hsv-1 By The Cgas-Sting Pathway In Microglia Orchestrates Antiviral Defence In The Cns, Line S. Reinert, Katarina Lopusna, Henriette Winther, Chenglong Sun, Martin K. Thomsen, Ramya Nandakumar, Trine H. Mogensen, Morten Meyer, Christian Vaegter, Jens R. Nyengaard, Katherine A. Fitzgerald, Soren R. Paludan
Sensing Of Hsv-1 By The Cgas-Sting Pathway In Microglia Orchestrates Antiviral Defence In The Cns, Line S. Reinert, Katarina Lopusna, Henriette Winther, Chenglong Sun, Martin K. Thomsen, Ramya Nandakumar, Trine H. Mogensen, Morten Meyer, Christian Vaegter, Jens R. Nyengaard, Katherine A. Fitzgerald, Soren R. Paludan
Katherine A. Fitzgerald
Herpes simplex encephalitis (HSE) is the most common form of acute viral encephalitis in industrialized countries. Type I interferon (IFN) is important for control of herpes simplex virus (HSV-1) in the central nervous system (CNS). Here we show that microglia are the main source of HSV-induced type I IFN expression in CNS cells and these cytokines are induced in a cGAS-STING-dependent manner. Consistently, mice defective in cGAS or STING are highly susceptible to acute HSE. Although STING is redundant for cell-autonomous antiviral resistance in astrocytes and neurons, viral replication is strongly increased in neurons in STING-deficient mice. Interestingly, HSV-infected microglia …