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 journalArticle

13 Citations (Scopus)

Abstract

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
JournalVirology
Volume499
DOIs
StatePublished - Dec 1 2016

Fingerprint

Dengue Virus
Dengue
Innate Immunity
Methylation
RNA
Dengue Vaccines
Infection
Genome
Immune Evasion
Interferon Type I
Virus Diseases
Culicidae
Point Mutation
Antiviral Agents
Viruses
Proteins

Keywords

  • Dengue virus
  • Innate immune response
  • Methyltransferase
  • NS5

ASJC Scopus subject areas

  • Virology

Cite this

Chang, D. C., Hoang, L. T., Mohamed Naim, A. N., Dong, H., Schreiber, M. J., Hibberd, M. L., ... Shi, P-Y. (2016). Evasion of early innate immune response by 2′-O-methylation of dengue genomic RNA. Virology, 499, 259-266. https://doi.org/10.1016/j.virol.2016.09.022

Evasion of early innate immune response by 2′-O-methylation of dengue genomic RNA. / Chang, David C.; Hoang, Long T.; Mohamed Naim, Ahmad Nazri; Dong, Hongping; Schreiber, Mark J.; Hibberd, Martin L.; Tan, Min Jie Alvin; Shi, Pei-Yong.

In: Virology, Vol. 499, 01.12.2016, p. 259-266.

Research output: Contribution to journalArticle

Chang, DC, Hoang, LT, Mohamed Naim, AN, Dong, H, Schreiber, MJ, Hibberd, ML, Tan, MJA & Shi, P-Y 2016, 'Evasion of early innate immune response by 2′-O-methylation of dengue genomic RNA', Virology, vol. 499, pp. 259-266. https://doi.org/10.1016/j.virol.2016.09.022
Chang DC, Hoang LT, Mohamed Naim AN, Dong H, Schreiber MJ, Hibberd ML et al. Evasion of early innate immune response by 2′-O-methylation of dengue genomic RNA. Virology. 2016 Dec 1;499:259-266. https://doi.org/10.1016/j.virol.2016.09.022
Chang, David C. ; Hoang, Long T. ; Mohamed Naim, Ahmad Nazri ; Dong, Hongping ; Schreiber, Mark J. ; Hibberd, Martin L. ; Tan, Min Jie Alvin ; Shi, Pei-Yong. / Evasion of early innate immune response by 2′-O-methylation of dengue genomic RNA. In: Virology. 2016 ; Vol. 499. pp. 259-266.
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