NDLI: A single nucleotide mutation in NS2A of Japanese encephalitis-live vaccine virus (SA14-14-2) ablates NS1' formation and contributes to attenuation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ye, Qing Li, Xiao-Feng Zhao, Hui Li, Shi-Hua Deng, Yong-Qiang Cao, Rui-Yuan Song, Ke-Yu Wang, Hong-Jiang Hua, Rong-Hong Yu, Yong-Xin Zhou, Xi Qin, E-De Qin, Cheng-Feng
Description	Author Affiliation: Ye Q ( Department of Virology, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China.)
Abstract	Japanese encephalitis (JE) remains the leading cause of viral encephalitis in the Asia-Pacific region, and the live vaccine SA14-14-2 is currently recommended by WHO and widely used in Asian countries with a good safety and efficacy profile. In this study, we demonstrated that SA14-14-2 failed to produce NS1', the larger NS1-related protein, compared with its parental strain SA14 in various cells. Sequence analysis and secondary structure prediction identified a single silent mutation G66A in the NS2A-coding region of SA14-14-2 destabilized the conserved pseudoknot structure, which was associated with a -1 ribosomal frame shift event. Using reverse genetic technology and animal study, we provided solid evidence that this single silent mutation G66A in the NS2A gene abolished the production of NS1' in vitro and reduced neurovirulence and neuroinvasiveness in mice. These findings provide critical information in understanding the molecular mechanism of JE vaccine attenuation and is critical for JE vaccine quality control.
File Format	HTM / HTML
ISSN	00221317
Issue Number	Pt 9
Volume Number	93
e-ISSN	14652099
Journal	Journal of General Virology
Language	English
Publisher	Microbiology Society
Publisher Date	2012-09-01
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Amino Acid Sequence Cell Line Research Support, Non-u.s. Gov't Viral Nonstructural Proteins Japanese Encephalitis Vaccines Discipline Virology Encephalitis Virus, Japanese Humans Virulence Mice, Inbred Balb C Molecular Sequence Data Male Metabolism Journal Article Virology Pathogenicity Point Mutation Chemistry Sequence Alignment Animals Vaccines, Attenuated Genetics Mice Encephalitis, Japanese
Content Type	Text
Resource Type	Article
Subject	Virology

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