ArticleNPJ vaccines2019
Japanese encephalitis vaccine-specific envelope protein E138K mutation does not attenuate virulence of West Nile virus.
Article in NPJ vaccines, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- A yellow fever 17D and Usutu virus chimera with rationally designed mutations in the envelope protein is lethal in an IfnarVirology journal · 2026Article
- Attenuating Mutations in Usutu Virus: Towards Understanding Orthoflavivirus Virulence Determinants and Live Attenuated Vaccine Design.Vaccines · 2025Article
- Identification of the flavivirus conserved residues in the envelope protein hinge region for the rational design of a candidate West Nile live-attenuated vaccine.NPJ vaccines · 2023Article
- Novel approaches for the rapid development of rationally designed arbovirus vaccines.One health (Amsterdam, Netherlands) · 2023Article
- Replication Kinetics of a Candidate Live-Attenuated Vaccine for Cache Valley Virus inVector borne and zoonotic diseases (Larchmont, N.Y.) · 2022Article
- Article
- Structure of Usutu virus SAAR-1776 displays fusion loop asymmetry.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Molecular Determinants of West Nile Virus Virulence and Pathogenesis in Vertebrate and Invertebrate Hosts.International journal of molecular sciences · 2020Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
West Nile (WNV) and Japanese encephalitis viruses (JEV) are closely related, mosquito-borne neurotropic flaviviruses. Although there are no licensed human vaccines for WNV, JEV has multiple human vaccines, including the live, attenuated vaccine SA14-14-2. Investigations into determinants of attenuation of JE SA14-14-2 demonstrated that envelope (E) protein mutation E138K was crucial to the attenuation of mouse virulence. As WNV is closely related to JEV, we investigated whether or not the E-E138K mutation would be beneficial to be included in a candidate live attenuated WNV vaccine. Rather than conferring a mouse attenuated phenotype, the WNV E-E138K mutant reverted and retained a wild-type mouse virulence phenotype. Next-generation sequencing analysis demonstrated that, although the consensus sequence of the mutant had the E-E138K mutation, there was increased variation in the E protein, including a single-nucleotide variant (SNV) revertant to the wild-type glutamic acid residue. Modeling of the E protein and analysis of SNVs showed that reversion was likely due to the inability of critical E-protein residues to be compatible electrostatically. Therefore, this mutation may not be reliable for inclusion in candidate live attenuated vaccines in related flaviviruses, such as WNV, and care must be taken in translation of attenuating mutations from one virus to another virus, even if they are closely related.
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