ArticleJournal of virology2013
Rational design of a flavivirus vaccine by abolishing viral RNA 2'-O methylation.
Article in Journal of virology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 90 citations in OpenAlex.
- Lost in translation: interferon-stimulated genes targeting flavivirus protein synthesis.Journal of virology · 2026Review
- The capping arms race: evolutionary interplay between IFIT proteins and viral molecular mimicry.Molecular biology reports · 2026Review
- Unraveling the complexities of neurotropic virus infection and immune evasion.Microbiology and molecular biology reviews : MMBR · 2025Review
- Dengue and Flavivirus Co-Infections: Challenges in Diagnosis, Treatment, and Disease Management.International journal of molecular sciences · 2025Review
- 2'-O-methyltransferase-deficient yellow fever virus: Restricted replication in the midgut and secondary tissues of Aedes aegypti mosquitoes severely limits dissemination.PLoS pathogens · 2024Article
- The Flavivirus Non-Structural Protein 5 (NS5): Structure, Functions, and Targeting for Development of Vaccines and Therapeutics.Vaccines · 2024Review
- A bioinformatics approach to systematically analyze the molecular patterns of monkeypox virus-host cell interactions.Heliyon · 2024Article
- A Stable Reverse Genetics System of Zika Virus Based on a Self-Splicing Group II Intron.Methods in molecular biology (Clifton, N.J.) · 2024Article
- A novel live attenuated duck Tembusu virus vaccine targeting N7 methyltransferase protects ducklings against pathogenic strains.Veterinary research · 2023Article
- Novel approaches for the rapid development of rationally designed arbovirus vaccines.One health (Amsterdam, Netherlands) · 2023Article
- The regulation of antiviral innate immunity through non-mFrontiers in immunology · 2023Review
- Targeting Type I Interferon Induction and Signaling: How Zika Virus Escapes from Host Innate Immunity.International journal of biological sciences · 2023Review
- Regulation of antiviral innate immunity by chemical modification of viral RNA.Wiley interdisciplinary reviews. RNA · 2022Review
- The infectivity and pathogenicity of hepatitis A virus live-attenuated vaccine strain H2 in type I interferon receptor-deficient mice.Virologica Sinica · 2022Article
- Review
- A Methyltransferase-Defective Vesicular Stomatitis Virus-Based SARS-CoV-2 Vaccine Candidate Provides Complete Protection against SARS-CoV-2 Infection in Hamsters.Journal of virology · 2021Article
- Review
- Zika Virus Pathogenesis: A Battle for Immune Evasion.Vaccines · 2021Review
- An immune epigenetic insight to COVID-19 infection.Epigenomics · 2021Review
- Methyltransferase-Deficient Avian Flaviviruses Are Attenuated Due to Suppression of Viral RNA Translation and Induction of a Higher Innate Immunity.Frontiers in immunology · 2021Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Viruses that replicate in the cytoplasm cannot access the host nuclear capping machinery. These viruses have evolved viral methyltransferase(s) to methylate N-7 and 2'-O cap of their RNA; alternatively, they "snatch" host mRNA cap to form the 5' end of viral RNA. The function of 2'-O methylation of viral RNA cap is to mimic cellular mRNA and to evade host innate immune restriction. A cytoplasmic virus defective in 2'-O methylation is replicative, but its viral RNA lacks 2'-O methylation and is recognized and eliminated by the host immune response. Such a mutant virus could be rationally designed as a live attenuated vaccine. Here, we use Japanese encephalitis virus (JEV), an important mosquito-borne flavivirus, to prove this novel vaccine concept. We show that JEV methyltransferase is responsible for both N-7 and 2'-O cap methylations as well as evasion of host innate immune response. Recombinant virus completely defective in 2'-O methylation was stable in cell culture after being passaged for >30 days. The mutant virus was attenuated in mice, elicited robust humoral and cellular immune responses, and retained the engineered mutation in vivo. A single dose of immunization induced full protection against lethal challenge with JEV strains in mice. Mechanistically, the attenuation phenotype was attributed to the enhanced sensitivity of the mutant virus to the antiviral effects of interferon and IFIT proteins. Collectively, the results demonstrate the feasibility of using 2'-O methylation-defective virus as a vaccine approach; this vaccine approach should be applicable to other flaviviruses and nonflaviviruses that encode their own viral 2'-O methyltransferases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.