Hepatitis C virus RNA is 5′-capped with flavin adenine dinucleotide

Anna V. Sherwood, Lizandro R. Rivera-Rangel, Line A. Ryberg, Helena S. Larsen, Klara M. Anker, Rui Costa, Cathrine B. Vågbø, Eva Jakljevič, Long V. Pham, Carlota Fernandez-Antunez, Gabriele Indrisiunaite, Agnieszka Podolska-Charlery, Julius E. R. Grothen, Nicklas W. Langvad, Nicolas Fossat, Anna Offersgaard, Amal Al-Chaer, Louise Nielsen, Anna Kuśnierczyk, Christina Sølund, Nina Weis, Judith M. Gottwein, Kenn Holmbeck, Sandro Bottaro, Santseharay Ramirez, Jens Bukh (), Troels K. H. Scheel () and Jeppe Vinther ()
Additional contact information
Anna V. Sherwood: University of Copenhagen
Lizandro R. Rivera-Rangel: Copenhagen University Hospital
Line A. Ryberg: Copenhagen University Hospital
Helena S. Larsen: Copenhagen University Hospital
Klara M. Anker: University of Copenhagen
Rui Costa: Copenhagen University Hospital
Cathrine B. Vågbø: Norwegian University of Science and Technology and the Central Norway Regional Health Authority
Eva Jakljevič: Copenhagen University Hospital
Long V. Pham: Copenhagen University Hospital
Carlota Fernandez-Antunez: Copenhagen University Hospital
Gabriele Indrisiunaite: University of Copenhagen
Agnieszka Podolska-Charlery: University of Copenhagen
Julius E. R. Grothen: University of Copenhagen
Nicklas W. Langvad: University of Copenhagen
Nicolas Fossat: Copenhagen University Hospital
Anna Offersgaard: Copenhagen University Hospital
Amal Al-Chaer: University of Copenhagen
Louise Nielsen: Copenhagen University Hospital
Anna Kuśnierczyk: Norwegian University of Science and Technology and the Central Norway Regional Health Authority
Christina Sølund: Copenhagen University Hospital
Nina Weis: Copenhagen University Hospital
Judith M. Gottwein: Copenhagen University Hospital
Kenn Holmbeck: Copenhagen University Hospital
Sandro Bottaro: University of Copenhagen
Santseharay Ramirez: Copenhagen University Hospital
Jens Bukh: Copenhagen University Hospital
Troels K. H. Scheel: Copenhagen University Hospital
Jeppe Vinther: University of Copenhagen

Nature, 2023, vol. 619, issue 7971, 811-818

Abstract: Abstract RNA viruses have evolved elaborate strategies to protect their genomes, including 5′ capping. However, until now no RNA 5′ cap has been identified for hepatitis C virus1,2 (HCV), which causes chronic infection, liver cirrhosis and cancer3. Here we demonstrate that the cellular metabolite flavin adenine dinucleotide (FAD) is used as a non-canonical initiating nucleotide by the viral RNA-dependent RNA polymerase, resulting in a 5′-FAD cap on the HCV RNA. The HCV FAD-capping frequency is around 75%, which is the highest observed for any RNA metabolite cap across all kingdoms of life4–8. FAD capping is conserved among HCV isolates for the replication-intermediate negative strand and partially for the positive strand. It is also observed in vivo on HCV RNA isolated from patient samples and from the liver and serum of a human liver chimeric mouse model. Furthermore, we show that 5′-FAD capping protects RNA from RIG-I mediated innate immune recognition but does not stabilize the HCV RNA. These results establish capping with cellular metabolites as a novel viral RNA-capping strategy, which could be used by other viruses and affect anti-viral treatment outcomes and persistence of infection.

Date: 2023
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-023-06301-3 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:619:y:2023:i:7971:d:10.1038_s41586-023-06301-3

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-023-06301-3

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().