ArticleJournal of virology2012
The attenuated genotype of varicella-zoster virus includes an ORF0 transitional stop codon mutation.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Serious neurological adverse events in immunocompetent children and adolescents caused by viral reactivation in the years following varicella vaccination.Reviews in medical virology · 2024Pooled it
- Genomic comparison reveals single-nucleotide polymorphic sites and attenuation-associated site combinations specific to Chinese live attenuated varicella-zoster virus vaccines.Human vaccines & immunotherapeutics · 2026Article
- Whole-genome sequence of a varicella-zoster strain from an immunocompetent pediatric patient with severe herpes zoster.Microbiology resource announcements · 2026Article
- Targeted metagenomics reveals hidden chickenpox epidemic amid Mpox surveillance in Uganda.Scientific reports · 2026Article
- Cancer viroimmunotherapy platforms based on varicella-zoster virus and cytomegalovirus.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- The live attenuated varicella-zoster virus vaccine vOka: Molecular and cellular biology of its skin attenuation.Human vaccines & immunotherapeutics · 2025Review
- Insights into pathologic mechanisms occurring during serious adverse events following live zoster vaccination.Journal of virology · 2025Review
- Upregulation of keratin 15 is required for varicella-zoster virus replication in keratinocytes and is attenuated in the live attenuated vOka vaccine strain.Virology journal · 2024Article
- Oncolytic varicella-zoster virus engineered with ORF8 deletion and armed with drug-controllable interleukin-12.Journal for immunotherapy of cancer · 2024Article
- Creating the "Dew Drop on a Rose Petal": the Molecular Pathogenesis of Varicella-Zoster Virus Skin Lesions.Microbiology and molecular biology reviews : MMBR · 2023Review
- Insights From Studies of the Genetics, Pathogenesis, and Immunogenicity of the Varicella Vaccine.The Journal of infectious diseases · 2022Article
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- Review
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- Alphaherpesvirus Vaccines.Current issues in molecular biology · 2021Review
- Twelve Children with Varicella Vaccine Meningitis: Neuropathogenesis of Reactivated Live Attenuated Varicella Vaccine Virus.Viruses · 2020Review
- Increase in the genetic polymorphism of varicella-zoster virus after passaging in in vitro cell culture.Journal of microbiology (Seoul, Korea) · 2019Article
- Comparison of the Whole-Genome Sequence of an Oka Varicella Vaccine from China with Other Oka Vaccine Strains Reveals Sites Putatively Critical for Vaccine Efficacy.Journal of virology · 2019Article
- Severe Herpes Zoster Following Varicella Vaccination in Immunocompetent Young Children.Journal of child neurology · 2019Article
- Molecular Aspects of Varicella-Zoster Virus Latency.Viruses · 2018Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
Varicella-zoster virus (VZV) is the first of the human herpesviruses to be attenuated and subsequently approved as a live vaccine to prevent varicella and herpes zoster. Both the attenuated VZV vaccine, called vaccine Oka or vOka, and the parental strain pOka have been completely sequenced. Yet the specific determinants of attenuation are uncertain. The open reading frame (ORF) with the most single nucleotide polymorphisms (SNPs), ORF62, encodes the regulatory protein IE62, but IE62 studies have failed to define a specific SNP associated with attenuation. We have completed next-generation sequencing of the VZV Ellen genome, a strain known to be highly attenuated by its very limited replication in human skin xenografts in the SCID mouse model of VZV pathogenesis. A comparative analysis of the Ellen sequence with all other complete VZV sequences was extremely informative. In particular, an unexpected finding was a stop codon mutation in Ellen ORF0 (herpes simplex virus UL56 homolog) identical to one found in vOka, combined with the absence of polymorphisms in most Ellen ORFs that were known to be mutated in vOka. The mutated ORF0 protein was also imaged in both two dimensions and three dimensions by confocal microscopy. The probability of two VZV strains not connected by a recent common ancestor having an identical ORF0 SNP by chance would be 1 × 10(-8), in other words, extremely unlikely. Taken together, these bioinformatics analyses strongly suggest that the stop codon ORF0 SNP is one of the determinants of the attenuation genotype of live VZV vaccines.
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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.