ArticlePLoS pathogens2007
A point mutation in a herpesvirus polymerase determines neuropathogenicity.
Article in PLoS pathogens, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
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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
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 222 citations in OpenAlex.
- Relationship between equine herpesvirus-1 viremia and abortion or equine herpesvirus myeloencephalopathy in domesticated horses: A systematic review.Journal of veterinary internal medicinePooled it
- Retrospective assessment of equine herpesvirus type 1 (EHV-1) genotype-associated clinical disease in Ontario.The Canadian veterinary journal = La revue veterinaire canadienne · 2026Article
- Nucleolar proteins nucleolin and nucleophosmin 1 differentially relocalize during equid alphaherpesvirus 1 (EHV1) infection.Veterinary research communications · 2026Article
- Cross-Species Analysis of Transcriptomic Response to Alpha-Herpesvirus Infection in Human, Bovine and Equine Cells.International journal of molecular sciences · 2026Article
- The HIV-1 Vpr R77Q mutant alters host apoptotic gene regulation in CD4+ T cells.Frontiers in cellular and infection microbiology · 2026Article
- Equine histones are mobilized within equid alphaherpesvirus 1 (EHV1) replication compartments.Journal of virology · 2025Article
- Equine Herpesvirus Infections: Treatment Progress and Challenges in Horses and Donkeys.Veterinary sciences · 2025Review
- Molecular Detection and Genetic Characteristics of Equine Herpesviruses 1 and 4 in Egypt.Veterinary medicine international · 2025Article
- Attenuation of the neuropathogenic equine herpesvirus type 1 strain Ab4p in hamsters by a single amino acid mutation (D752N) in viral DNA polymerase ORF30.The Journal of veterinary medical science · 2024Article
- Divergent strains of EHV-1 in Swedish outbreaks during 2012 to 2021.BMC veterinary research · 2024Article
- Molecular Evolution of Protein Sequences and Codon Usage in Monkeypox Viruses.Genomics, proteomics & bioinformatics · 2024Article
- A Screening Study Identified Decitabine as an Inhibitor of Equid Herpesvirus 4 That Enhances the Innate Antiviral Response.Viruses · 2024Article
- Impact of the host immune response on the development of equine herpesvirus myeloencephalopathy in horses.The Journal of general virology · 2024Article
- Modulation of Equid Herpesvirus-1 Replication DynamicsViruses · 2024Article
- Molecular Detection of Equine Herpesviruses from Field Outbreaks in Donkeys in Northwest Amhara Region, Ethiopia.Veterinary medicine international · 2024Article
- Phylogenomic assessment of 23 equid alphaherpesvirus 1 isolates obtained from USA-based equids.Virology journal · 2023Article
- Anti-inflammatory compounds reduce equine herpesvirus type 1 replication and cell-to-cell spread.Frontiers in veterinary science · 2023Article
- Mutations in the monkeypox virus replication complex: Potential contributing factors to the 2022 outbreak.Journal of autoimmunity · 2022Article
- Infection with a Recently Discovered Gammaherpesvirus Variant in European Badgers,Pathogens (Basel, Switzerland) · 2022Article
- Molecular characteristics and pathogenicity of an equid alphaherpesvirus 1 strain isolated in China.Virus genes · 2022Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Infection with equid herpesvirus type 1 (EHV-1) leads to respiratory disease, abortion, and neurologic disorders in horses. Molecular epidemiology studies have demonstrated that a single nucleotide polymorphism resulting in an amino acid variation of the EHV-1 DNA polymerase (N752/D752) is significantly associated with the neuropathogenic potential of naturally occurring strains. To test the hypothesis that this single amino acid exchange by itself influences neuropathogenicity, we generated recombinant viruses with differing polymerase sequences. Here we show that the N752 mutant virus caused no neurologic signs in the natural host, while the D752 virus was able to cause inflammation of the central nervous system and ataxia. Neurologic disease induced by the D752 virus was concomitant with significantly increased levels of viremia (p = 0.01), but the magnitude of virus shedding from the nasal mucosa was similar between the N752 and D752 viruses. Both viruses replicated with similar kinetics in fibroblasts and epithelial cells, but exhibited differences in leukocyte tropism. Last, we observed a significant increase (p < 0.001) in sensitivity of the N752 mutant to aphidicolin, a drug targeting the viral polymerase. Our results demonstrate that a single amino acid variation in a herpesvirus enzyme can influence neuropathogenic potential without having a major effect on virus shedding from infected animals, which is important for horizontal spread in a population. This observation is very interesting from an evolutionary standpoint and is consistent with data indicating that the N752 DNA pol genotype is predominant in the EHV-1 population, suggesting that decreased viral pathogenicity in the natural host might not be at the expense of less efficient inter-individual transmission.
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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.