ArticlePLoS pathogens2016
Quantitative Trait Locus Based Virulence Determinant Mapping of the HSV-1 Genome in Murine Ocular Infection: Genes Involved in Viral Regulatory and Innate Immune Networks Contribute to Virulence.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 39 citations in OpenAlex.
- Herpes simplex virus type-1 ocular infection in thrombospondin-1 deficient C57BL/6J mice.PloS one · 2026Article
- Viral Genomic Variation and the Severity of Genital Herpes Simplex Virus-2 Infection as Quantified by Shedding Rate: A Viral Genome-Wide Association Study.The Journal of infectious diseases · 2024Article
- UVB induced reactivation leads to HSV1 in the corneas of virtually all latently infected mice and requires STING to develop corneal disease.Scientific reports · 2024Article
- Development and immunogenicity evaluation of a quadruple-gene-deleted pseudorabies virus strain.Frontiers in microbiology · 2024Article
- Phylogenetic and Genomic Characterization of Whole Genome Sequences of Ocular Herpes Simplex Virus Type 1 Isolates Identifies Possible Virulence Determinants in Humans.Investigative ophthalmology & visual science · 2023Article
- Disease parameters following ocular herpes simplex virus type 1 infection are similar in male and female BALB/C mice.PloS one · 2023Article
- Whole exome sequencing of patients with varicella-zoster virus and herpes simplex virus induced acute retinal necrosis reveals rare disease-associated genetic variants.Frontiers in molecular neuroscience · 2023Article
- Mechanism of herpesvirus UL24 protein regulating viral immune escape and virulence.Frontiers in microbiology · 2023Review
- Multi-phenotype analysis for enhanced classification of 11 herpes simplex virus 1 strains.The Journal of general virology · 2022Article
- Entry receptor bias in evolutionarily distant HSV-1 clinical strains drives divergent ocular and nervous system pathologies.The ocular surface · 2021Article
- Genome Sequence of the Virulent Model Herpes Simplex Virus 1 Strain McKrae Demonstrates the Presence of at Least Two Widely Used Variant Strains.Microbiology resource announcements · 2021Article
- Alphaherpesvirus Genomics: Past, Present and Future.Current issues in molecular biology · 2021Review
- "Non-Essential" Proteins of HSV-1 with Essential Roles In Vivo: A Comprehensive Review.Viruses · 2020Review
- Herpes Simplex Virus Mistyping due to HSV-1 × HSV-2 Interspecies Recombination in Viral Gene Encoding Glycoprotein B.Viruses · 2020Article
- Whole genome sequencing of Herpes Simplex Virus 1 directly from human cerebrospinal fluid reveals selective constraints in neurotropic viruses.Virus evolution · 2020Article
- Personalized viral genomic investigation of herpes simplex virus 1 perinatal viremic transmission with dual fatality.Cold Spring Harbor molecular case studies · 2019Article
- Review
- Comparison of Herpes Simplex Virus 1 Strains Circulating in Finland Demonstrates the Uncoupling of Whole-Genome Relatedness and Phenotypic Outcomes of Viral Infection.Journal of virology · 2019Article
- Viral Genetics Modulate Orolabial Herpes Simplex Virus Type 1 Shedding in Humans.The Journal of infectious diseases · 2019Article
- Herpes Simplex Virus Disease Management and Diagnostics in the Era of High-Throughput Sequencing.Clinical microbiology newsletter · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Herpes simplex virus type 1 causes mucocutaneous lesions, and is the leading cause of infectious blindness in the United States. Animal studies have shown that the severity of HSV-1 ocular disease is influenced by three main factors; innate immunity, host immune response and viral strain. We previously showed that mixed infection with two avirulent HSV-1 strains (OD4 and CJ994) resulted in recombinants that exhibit a range of disease phenotypes from severe to avirulent, suggesting epistatic interactions were involved. The goal of this study was to develop a quantitative trait locus (QTL) analysis of HSV-1 ocular virulence determinants and to identify virulence associated SNPs. Blepharitis and stromal keratitis quantitative scores were characterized for 40 OD4:CJ994 recombinants. Viral titers in the eye were also measured. Virulence quantitative trait locus mapping (vQTLmap) was performed using the Lasso, Random Forest, and Ridge regression methods to identify significant phenotypically meaningful regions for each ocular disease parameter. The most predictive Ridge regression model identified several phenotypically meaningful SNPs for blepharitis and stromal keratitis. Notably, phenotypically meaningful nonsynonymous variations were detected in the UL24, UL29 (ICP8), UL41 (VHS), UL53 (gK), UL54 (ICP27), UL56, ICP4, US1 (ICP22), US3 and gG genes. Network analysis revealed that many of these variations were in HSV-1 regulatory networks and viral genes that affect innate immunity. Several genes previously implicated in virulence were identified, validating this approach, while other genes were novel. Several novel polymorphisms were also identified in these genes. This approach provides a framework that will be useful for identifying virulence genes in other pathogenic viruses, as well as epistatic effects that affect HSV-1 ocular virulence.
Indexed as
Identifiers
What OpenQuestion holds
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.