An effective vaccine for the hepatitis C virus (HCV) remains an unmet medical need. There is no animal model for assessing HCV vaccines; however, rodent hepacivirus (RHV) infection in laboratory rats recapitulates the lifelong chronic hepatotropic infection and immune evasion of HCV. Here, we designed a live-attenuated vaccine (LAV) for RHV and determined its immunogenicity and efficacy for preventing chronic infection.
View Article and Find Full Text PDFCpG dinucleotides are under-represented in the genomes of most RNA viruses. Synonymously increasing CpG content of a range of RNA virus genomes reliably causes replication defects due to the recognition of CpG motifs in RNA by cellular Zinc-finger Antiviral Protein (ZAP). Prior to the discovery of ZAP as a CpG sensor, we described an engineered influenza A virus (IAV) enriched for CpGs in segment 5 that displays the expected replication defects.
View Article and Find Full Text PDFDuring the 56th annual meeting of the International Committee on Taxonomy of Viruses (ICTV), held in Bari, Italy, in August 2024, two technical proposals were presented. The first called for amended versions of accepted taxonomic proposals to be named in such a way to ensure that they are readily accessible on the ICTV website (2024.001G).
View Article and Find Full Text PDFTaxonomic classification of cellular organisms requires the publication of descriptions and proposed names of species and the deposition of specimens. Virus taxonomy is developed through a different system of annual submission of formal taxonomy proposals (TPs) that can be submitted by anyone but are typically prepared by a study group appointed by the International Committee on Taxonomy of Viruses (ICTV) and consisting of experts on a particular group of viruses. These are initially evaluated by an expert subcommittee and by the executive committee (EC) of the ICTV.
View Article and Find Full Text PDFIn April 2024, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum was expanded by 1 new order, 1 new family, 6 new subfamilies, 34 new genera and 270 new species. One class, two orders and six species were renamed. Seven families and 12 genera were moved; ten species were renamed and moved; and nine species were abolished.
View Article and Find Full Text PDFBackground: Sensitive molecular detection of hepatitis B virus (HBV) DNA is crucial for diagnosing and managing occult hepatitis. To improve the sensitivity of HBV DNA detection, we compared the effectiveness of polyethylene glycol (PEG) precipitation and ultracentrifugation to concentrate DNA prior to extraction.
Methods: Twenty-three HBV DNA-positive samples with low viral loads were compared between the extraction of standard (0.
Virus taxonomy, comprising classification and nomenclature, is regulated by the International Committee on Taxonomy of Viruses (ICTV). Taxon names are standardized to facilitate recognition and communication, with defined suffixes for each rank (e.g.
View Article and Find Full Text PDFBackground: Enterovirus D68 (EV-D68) causes respiratory disease ranging from mild to severe and in rare cases a paralytic syndrome, called acute flaccid myelitis (AFM). Since the global EV-D68 outbreak in 2014, the virus has mainly circulated in biennial epidemic cycles with peaks detected during even years. However, following the COVID-19 pandemic, the seasonal pattern of EV-D68 has been characterized by large yearly upsurges.
View Article and Find Full Text PDFEClinicalMedicine
March 2025
The implementation of effective blood donation screening for hepatitis B virus (HBV) anti-core antibodies with highly sensitive molecular HBV DNA detection in low-endemic countries like the United Kingdom has improved blood safety. However, the linkage to care and management for blood donors with occult HBV infection (OBI) is a complex dilemma involving virological, clinical, methodological, and social issues. Limited evidence suggests that OBI may accelerate the progression of liver disease and cancer.
View Article and Find Full Text PDFThe are a family of non-segmented positive-sense enveloped RNA viruses containing significant pathogens including hepatitis C virus and yellow fever virus. Recent large-scale metagenomic surveys have identified many diverse RNA viruses related to classical orthoflaviviruses and pestiviruses but quite different genome lengths and configurations, and with a hugely expanded host range that spans multiple animal phyla, including molluscs, cnidarians and stramenopiles,, and plants. Grouping of RNA-directed RNA polymerase (RdRP) hallmark gene sequences of flavivirus and 'flavi-like' viruses into four divergent clades and multiple lineages within them was congruent with helicase gene phylogeny, PPHMM profile comparisons, and comparison of RdRP protein structure predicted by AlphFold2.
View Article and Find Full Text PDFBackground: Estimates of Lyme disease incidence in England are based on reporting of cases with a laboratory-confirmed diagnosis only, underestimating total cases. In 2017 - 2018, two independent reviews commissioned by the UK Government highlighted the lack of official data on Lyme disease prevalence and incidence as a critical knowledge gap.
Aim: To estimate the prevalence of IgG antibodies in the English adult population specific for Borrelia burgdorferi sensu lato (Bbsl), the causative agent of Lyme disease.
Objectives: Convalescent plasma (CP) treatment of COVID-19 has shown significant therapeutic effect only when administered early. We investigated the importance of patient and CP seroprofiles on treatment outcome in REMAP-CAP CP trial.
Methods: We evaluated neutralising antibodies (nAb), anti-spike (S) IgM, IgG, IgG avidity, IgG fucosylation and respiratory viral loads in a sub-set of patients (n=80) and controls (n=51) before and after transfusion, comparing them to those in the CP units (n=157) they received.
Taxonomic classification of viruses is essential for understanding their evolution. Genomic classification of viruses at higher taxonomic ranks, such as order or phylum, is typically based on alignment and comparison of amino acid sequence motifs in conserved genes. Classification at lower taxonomic ranks, such as genus or species, is usually based on nucleotide sequence identities between genomic sequences.
View Article and Find Full Text PDFBackground: Pathogen reduction technology (PRT) is an intervention designed to proactively reduce the amount of known and unknown pathogens in donated blood. As current screening for known pathogens is highly effective, some previous evaluations have found that the value of PRT largely hinges on a previously unknown pathogen, most likely a novel virus, emerging and entering the blood supply. In such situations, the risk of emergence can and should be modeled and presented transparently in the cost-effectiveness results for deliberation by decision-makers.
View Article and Find Full Text PDFThe International Committee for the Taxonomy of Viruses (ICTV) regulates assignment and names of virus species and higher taxa through its taxonomy proposal and ratification process. Despite using similar taxonomic ranks to those used elsewhere in biology, the ICTV has maintained the principle that species and other taxa are strictly categories with a formal nomenclature, whereas the viruses as objects are referenced through a parallel inventory of community-assigned virus names. This is strikingly different from common and scientific name synonyms for species used elsewhere in biology.
View Article and Find Full Text PDFEnterovirus A71 (EV-A71) and coxsackievirus A6 (CVA6) primarily cause hand, foot and mouth disease and have emerged to cause potential fatal neurological and systemic manifestations. However, limited surveillance data collected through passive surveillance systems hampers characterization of their epidemiological dynamics. We fit a series of catalytic models to age-stratified seroprevalence data for EV-A71 and CVA6 collected in England at three time points (2006, 2011 and 2017) to estimate the force of infection (FOI) over time and assess possible changes in transmission.
View Article and Find Full Text PDFUnlabelled: The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the pandemic and post-pandemic periods has been characterized by rapid adaptive changes that confer immune escape and enhanced human-to-human transmissibility. Sequence change is additionally marked by an excess number of C→U transitions suggested as being due to host-mediated genome editing. To investigate how these influence the evolutionary trajectory of SARS-CoV-2, 2,000 high-quality, coding complete genome sequences of SARS-CoV-2 variants collected pre-September 2020 and from each subsequently appearing alpha, delta, BA.
View Article and Find Full Text PDFNucleic Acids Res
November 2024
The viral intra-host genetic diversities and interactions with the human genome during decades of persistence remain poorly characterized. In this study, we analyzed the variability and integration sites of persisting viruses in nine organs from thirteen individuals who died suddenly from non-viral causes. The viruses studied included parvovirus B19, six herpesviruses, Merkel cell (MCPyV) and JC polyomaviruses, totaling 127 genomes.
View Article and Find Full Text PDFBioinformatics
October 2024
Motivation: Target enrichment strategies generate genomic data from multiple pathogens in a single process, greatly improving sensitivity over metagenomic sequencing and enabling cost-effective, high-throughput surveillance and clinical applications. However, uptake by research and clinical laboratories is constrained by an absence of computational tools that are specifically designed for the analysis of multi-pathogen enrichment sequence data. Here we present an analysis pipeline, Castanet, for use with multi-pathogen enrichment sequencing data.
View Article and Find Full Text PDFObjectives: We evaluated the extent of virus heterogeneity in PeV infected infants in the UK, Canada and Australia.
Methods: Samples were collected from PeV infected infants during 2013-16. Next generation sequencing was used to obtain sequencing data and construct phylogenetic trees based on analysis of the VP1 region.
Factor VIII and IX clotting factor concentrates manufactured from pooled plasma have been identified as potent sources of virus infection in persons with hemophilia (PWHs) in the 1970s and 1980s. To investigate the range and diversity of viruses over this period, we analysed 24 clotting factor concentrates for several blood-borne viruses. Nucleic acid was extracted from 14 commercially produced clotting factors and 10 from nonremunerated donors, preserved in lyophilized form (expiry dates: 1974-1992).
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