Biochemical and genetic characterization of dengue virus methyltransferase

Hongping Dong, David C. Chang, Xuping Xie, Ying Xiu Toh, Ka Yan Chung, Gang Zou, Julien Lescar, Siew Pheng Lim, Pei Yong Shi

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

We report that dengue virus (DENV) methyltransferase sequentially methylates the guanine N-7 and ribose 2'-O positions of viral RNA cap (GpppA→m7GpppA→m7GpppAm). The order of two methylations is determined by the preference of 2'-O methylation for substrate m7GpppA-RNA to GpppA-RNA, and the 2'-O methylation is not absolutely dependent on the prior N-7 methylation. A mutation that completely abolished the 2'-O methylation attenuated DENV replication in cell culture, whereas another mutation that abolished both methylations was lethal for viral replication, suggesting that N-7 methylation is more important than 2'-O methylation in viral replication. The latter mutant with lethal replication could be rescued by trans complementation using a wild-type DENV replicon. Furthermore, we found that chimeric DENVs containing the West Nile virus methyltransferase, polymerase, or full-length NS5 were nonreplicative, but the replication defect could also be rescued through trans complementation using the wild-type DENV replicon.

Original languageEnglish (US)
Pages (from-to)568-578
Number of pages11
JournalVirology
Volume405
Issue number2
DOIs
StatePublished - Sep 30 2010

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Keywords

  • Antiviral target
  • Dengue virus
  • Flavivirus replication
  • Methyltransferase
  • RNA cap methylation

ASJC Scopus subject areas

  • Virology

Cite this

Dong, H., Chang, D. C., Xie, X., Toh, Y. X., Chung, K. Y., Zou, G., Lescar, J., Lim, S. P., & Shi, P. Y. (2010). Biochemical and genetic characterization of dengue virus methyltransferase. Virology, 405(2), 568-578. https://doi.org/10.1016/j.virol.2010.06.039