The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
West Nile Virus 5′-Cap Structure Is Formed by Sequential Guanine N-7 and Ribose 2′-O Methylations by Nonstructural Protein 5
Open accessAbstract
Many flaviviruses are globally important human pathogens. Their plus-strand RNA genome contains a 5′-cap structure that is methylated at the guanine N-7 and the ribose 2′-OH positions of the first transcribed nucleotide, adenine (m 7 GpppAm). Using West Nile virus (WNV), we demonstrate, for the first time, that the nonstructural protein 5 (NS5) mediates both guanine N-7 and ribose 2′-O methylations and therefore is essential for flavivirus 5′-cap formation. We show that a recombinant full-length and a truncated NS5 protein containing the methyltransferase (MTase) domain methylates GpppA-capped and m 7 GpppA-capped RNAs to m 7 GpppAm-RNA, using S -adenosylmethionine as a methyl donor. Furthermore, methylation of GpppA-capped RNA sequentially yielded m 7 GpppA- and m 7 GpppAm-RNA products, indicating that guanine N-7 precedes ribose 2′-O methylation. Mutagenesis of a K 61 -D 146 -K 182 -E 218 tetrad conserved in other cellular and viral MTases suggests that NS5 requires distinct amino acids for its N-7 and 2′-O MTase activities. The entire K 61 -D 146 -K 182 -E 218 motif is essential for 2′-O MTase activity, whereas N-7 MTase activity requires only D 146 . The other three amino acids facilitate, but are not essential for, guanine N-7 methylation. Amino acid substitutions within the K 61 -D 146 -K 182 -E 218 motif in a WNV luciferase-reporting replicon significantly reduced or abolished viral replication in cells. Additionally, the mutant MTase-mediated replication defect could not be trans complemented by a wild-type replicase complex. These findings demonstrate a critical role for the flavivirus MTase in viral reproduction and underscore this domain as a potential target for antiviral therapy.
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Cites
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Structure of the Neurospora SET Domain Protein DIM-5, a Histone H3 Lysine Methyltransferase
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Self-citationInfectious cDNA Clone of the Epidemic West Nile Virus from New York City
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Self-citationStructural Basis for Sequence-Nonspecific Recognition of 5′-Capped mRNA by a Cap-Modifying Enzyme
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The Global Ecology and Epidemiology of West Nile Virus
Chancey, C., Grinev, A., Volkova, E., & Rios, M. (2015) · BioMed Research International · doi:10.1155/2015/376230 · Cited by 607
In Vitro Reconstitution of SARS-Coronavirus mRNA Cap Methylation
Bouvet, M., Debarnot, C., Imbert, I., Selisko, B., Snijder, E. J., Canard, B., & Decroly, E. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000863 · Cited by 406
Structure and Function of Flavivirus NS5 Methyltransferase
Zhou, Y., Ray, D., Zhao, Y., Dong, H., Ren, S., Li, Z., Guo, Y., Bernard, K. A., Shi, P.-Y., & Li, H. (2007) · Journal of Virology · doi:10.1128/jvi.02704-06 · Cited by 406
Self-citationBiochemistry and Molecular Biology of Flaviviruses
Barrows, N. J., Campos, R. K., Liao, K.-C., Prasanth, K. R., Soto-Acosta, R., Yeh, S.-C., Schott-Lerner, G., Pompon, J., Sessions, O. M., Bradrick, S. S., et al. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00719 · Cited by 341
Japanese encephalitis: The virus and vaccines
Yun, S.-I., & Lee, Y.-M. (2014) · Human Vaccines & Immunotherapeutics · doi:10.4161/hv.26902 · Cited by 288
Metadata
- Authors
- Ray, D., Shah, A., Tilgner, M., Guo, Y., Zhao, Y., Dong, H., Deas, T. S., Zhou, Y., Li, H., & Shi, P.-Y.
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2006-09
- Volume
- 80
- Issue
- 17
- Pages
- 8362-8370
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- OpenAlex
- W2107132989
- Cited by
- 386
- References
- 23
- FWCI
- 17.40
- Type
- journal article
- Language
- en
- Open access
- green
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- Ray, D., Shah, A., Tilgner, M., Guo, Y., Zhao, Y., Dong, H., Deas, T. S., Zhou, Y., Li, H., & Shi, P.-Y. (2006). West Nile Virus 5′-Cap Structure Is Formed by Sequential Guanine N-7 and Ribose 2′-O Methylations by Nonstructural Protein 5. Journal of Virology. https://doi.org/10.1128/jvi.00814-06
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