title: Evasion of early innate immune response by 2'-O-methylation of dengue genomic RNA.
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.
authors.affiliation: Novartis Institute of Tropical Diseases, Singapore.
authors.forename: David C
authors.initials: DC
authors.lastname: Chang
authors.affiliation: Infectious Diseases, Genome Institute of Singapore, Singapore.
authors.forename: Long T
authors.initials: LT
authors.lastname: Hoang
authors.affiliation: Infectious Diseases, Genome Institute of Singapore, Singapore.
authors.forename: Ahmad Nazri
authors.initials: AN
authors.lastname: Mohamed Naim
authors.affiliation: Novartis Institute of Tropical Diseases, Singapore.
authors.forename: Hongping
authors.initials: H
authors.lastname: Dong
authors.affiliation: Novartis Institute of Tropical Diseases, Singapore.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Schreiber
authors.affiliation: Infectious Diseases, Genome Institute of Singapore, Singapore; Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hibberd
authors.affiliation: Infectious Diseases, Genome Institute of Singapore, Singapore. Electronic address: tanmja@gis.a-star.edu.sg.
authors.forename: Min Jie Alvin
authors.initials: MJA
authors.lastname: Tan
authors.affiliation: Novartis Institute of Tropical Diseases, Singapore; Department of Biochemistry and Molecular Biology, Department of Pharmacology and Toxicology, Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: peshi@utmb.edu.
authors.forename: Pei-Yong
authors.initials: PY
authors.lastname: Shi
mesh_terms: D002460:Cell Line; D019175:DNA Methylation; D003715:Dengue / Q000276:immunology* / Q000821:virology; D003716:Dengue Virus / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D023281:Genomics; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics* / Q000276:immunology
chemical_list: D012367:RNA, Viral
keywords: Dengue virus; Innate immune response; Methyltransferase; NS5