γHV68 vGAT: a viral pseudoenzyme pimping for PAMPs
Autor: | Daniel Kolakofsky, Dominique Garcin |
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Rok vydání: | 2015 |
Předmět: |
Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor/immunology
viruses DEAD-box RNA Helicases/immunology chemical and pharmacologic phenomena Biology Article DEAD-box RNA Helicases Viral Proteins Gammaherpesvirinae Herpes virus Animals Humans Receptors Immunologic Deamidation Molecular Biology Immune Evasion ddc:616 Immune Evasion/genetics Innate immune system virus diseases Cell Biology RNA Viral/immunology biochemical phenomena metabolism and nutrition 3. Good health Metabolic enzymes Immunology DEAD Box Protein 58 RNA Viral Viral Proteins/immunology Carbon-Nitrogen Ligases with Glutamine as Amide-N-Donor biological phenomena cell phenomena and immunity Gammaherpesvirinae/immunology |
Zdroj: | Molecular Cell, Vol. 58, No 1 (2015) pp. 3-4 Molecular cell |
ISSN: | 1097-4164 1097-2765 |
Popis: | RIG-I is a pattern recognition receptor that senses viral RNA and is crucial for host innate immune defense. Here we describe a mechanism of RIG-I activation through amidotransferase-mediated deamidation. We show that viral homologues of phosphoribosylformyglycinamide synthase (PFAS), although lacking intrinsic enzyme activity, recruit cellular PFAS to deamidate and activate RIG-I. Accordingly, depletion and biochemical inhibition of PFAS impair RIG-I deamidation and concomitant activation. Purified PFAS and viral homologue thereof deamidate RIG-I in vitro. Ultimately, herpesvirus hijacks activated RIG-I to avoid antiviral cytokine production; loss of RIG-I or inhibition of RIG-I deamidation results in elevated cytokine production. Together, these findings demonstrate a surprising mechanism of RIG-I activation that is mediated by an enzyme. |
Databáze: | OpenAIRE |
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