Evasion of early innate immune response by 2′-O-methylation of dengue genomic RNA

David C. Chang, Long T. Hoang, Ahmad Nazri Mohamed Naim, Hongping Dong, Mark J. Schreiber, Martin L. Hibberd, Min Jie Alvin Tan, Pei Yong Shi

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Dengue virus (DENV) is the most prevalent mosquito-borne virus pathogen in humans. There is currently no antiviral therapeutic or widely available vaccine against dengue infection. The DENV RNA genome is methylated on its 5′ cap by its NS5 protein. DENV bearing a single E216A point mutation in NS5 loses 2′-O-methylation of its genome. While this mutant DENV is highly attenuated and immunogenic, the mechanism of this attenuation has not been elucidated. In this study, we find that replication of this mutant DENV is attenuated very early during infection. This early attenuation is not dependent on a functional type I interferon response and coincides with early activation of the innate immune response. Taken together, our data suggest that 2′-O-methylation of DENV genomic RNA is important for evasion of the host immune response during the very early stages of infection as the virus seeks to establish infection.

Original languageEnglish (US)
Pages (from-to)259-266
Number of pages8
StatePublished - Dec 1 2016


  • Dengue virus
  • Innate immune response
  • Methyltransferase
  • NS5

ASJC Scopus subject areas

  • Virology


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