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Targeting the viral Achilles' heel: recognition of 5'-triphosphate RNA in innate anti-viral defence.

ABSTRACT: Some RNA virus genomes bear 5'-triphosphates, which can be recognized in the cytoplasm of infected cells by host proteins that mediate anti-viral immunity. Both the innate sensor RIG-I and the interferon-induced IFIT proteins bind to 5'-triphosphate viral RNAs. RIG-I signals for induction of interferons during RNA virus infection while IFITs sequester viral RNAs to exert an anti-viral effect. Notably, the structures of these proteins reveal both similarities and differences, which are suggestive of independent evolution towards ligand binding. 5'-triphosphates, which are absent from most RNAs in the cytosol of uninfected cells, are thus a marker of virus infection that is targeted by the innate immune system for both induction and execution of the anti-viral response.

SUBMITTER: Rehwinkel J

PROVIDER: S-EPMC7185528 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Targeting the viral Achilles' heel: recognition of 5'-triphosphate RNA in innate anti-viral defence.

Rehwinkel Jan J Reis e Sousa Caetano C

Current opinion in microbiology 20130523 4

Some RNA virus genomes bear 5'-triphosphates, which can be recognized in the cytoplasm of infected cells by host proteins that mediate anti-viral immunity. Both the innate sensor RIG-I and the interferon-induced IFIT proteins bind to 5'-triphosphate viral RNAs. RIG-I signals for induction of interferons during RNA virus infection while IFITs sequester viral RNAs to exert an anti-viral effect. Notably, the structures of these proteins reveal both similarities and differences, which are suggestive ...[more]

PMID: 23707340

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Project description:The glycans on enveloped viruses are synthesized by host-cell machinery. Some of these glycans on zoonotic viruses of mammalian reservoirs are recognized by human natural antibodies that may protect against such viruses. These antibodies are produced mostly against carbohydrate antigens on gastrointestinal bacteria and fortuitously, they bind to carbohydrate antigens synthesized in other mammals, neutralize and destroy viruses presenting these antigens. Two such antibodies are: anti-Gal binding to ?-gal epitopes synthesized in non-primate mammals, lemurs, and New World monkeys, and anti-N-glycolyl neuraminic acid (anti-Neu5Gc) binding to N-glycolyl-neuraminic acid (Neu5Gc) synthesized in apes, Old World monkeys, and many non-primate mammals. Anti-Gal appeared in Old World primates following accidental inactivation of the ?1,3galactosyltransferase gene 20-30 million years ago. Anti-Neu5Gc appeared in hominins following the inactivation of the cytidine-monophosphate-N-acetyl-neuraminic acid hydroxylase gene, which led to the loss of Neu5Gc <6 million-years-ago. It is suggested that an epidemic of a lethal virus eliminated ancestral Old World-primates synthesizing ?-gal epitopes, whereas few mutated offspring lacking ?-gal epitopes and producing anti-Gal survived because anti-Gal destroyed viruses presenting ?-gal epitopes, following replication in parental populations. Similarly, anti-Neu5Gc protected few mutated hominins lacking Neu5Gc in lethal virus epidemics that eliminated parental hominins synthesizing Neu5Gc. Since ?-gal epitopes are presented on many zoonotic viruses it is suggested that vaccines elevating anti-Gal titers may be of protective significance in areas endemic for such zoonotic viruses. This protection would be during the non-primate mammal to human virus transmission, but not in subsequent human to human transmission where the virus presents human glycans. In addition, production of viral vaccines presenting multiple ?-gal epitopes increases their immunogenicity because of effective anti-Gal-mediated targeting of vaccines to antigen presenting cells for extensive uptake of the vaccine by these cells.

Dataset Information

Targeting the viral Achilles' heel: recognition of 5'-triphosphate RNA in innate anti-viral defence.

Publications

Targeting the viral Achilles' heel: recognition of 5'-triphosphate RNA in innate anti-viral defence.

Similar Datasets

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