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Hepatitis C virus RNA is 5’ flavin adenine dinucleotide (FAD) capped

ABSTRACT: RNA viruses have developed elaborate strategies for 5’ capping and protection of their genomes. However, so far no 5’ RNA cap has been identified for Hepatitis C virus (HCV), which cause chronic infection, liver cirrhosis and cancer in humans4. Here, we demonstrate that the cellular metabolite flavin adenine dinucleotide (FAD) is used as noncanonical initiating nucleotide by the viral RNA-dependent RNA polymerase resulting in a 5’ FAD cap on the HCV RNA. FAD capping is completely conserved for the HCV replication intermediate negative RNA strand and partially for the positive RNA strand. The prototype strain J6/JFH1 RNA is FAD capped when isolated from the liver and serum of a human liver chimeric mouse model and in vitro the FAD capping frequency is ~75 %, which is the highest metabolite RNA capping frequency observed. Furthermore, we show that 5’ FAD capping protects RNA from cell-intrinsic innate immune recognition but has limited effect on HCV RNA stability. These results establish capping with cellular metabolites, such as FAD, as a novel viral RNA capping and immune evasion strategy, which potentially could be used by many viruses for protection of their intermediate RNA strands and thereby affect viral treatment outcomes and persistency.

ORGANISM(S): Tick-borne encephalitis virus Bos taurus Hepacivirus hominis Bovine viral diarrhea virus 1-NADL Homo sapiens Chikungunya virus

PROVIDER: GSE180956 | GEO | 2022/07/31

REPOSITORIES: GEO

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