Biology subjects

Weir, W.

Publications and source records attributed to Weir, W..

4 recordsLinked to original sources

bioRxiv2026

Feline calicivirus encoding NanoLuc luciferase as a tool for assessing antibody neutralisation and antivirals

Feline calicivirus (FCV) is among the most common viruses to infect cats worldwide, with prevalence estimated to range from 10-90% depending on the population sampled. Typical FCV infection presents with oral ulcerations, fever and in some cases can also lead to clinical signs such as pneumonia or "limping syndrome". However, some FCV strains have been isolated from cats exhibiting virulent systemic (VS) disease, which is associated with high morbidity and mortality. Breakthrough VS-FCV infections have been recorded in vaccinated cats and, therefore, there is considerable interest in developing novel therapeutics for use in the face of VS-FCV outbreaks. However, to design effective therapeutics, a tractable system to systematically assess the efficacy of novel vaccine candidates or antivirals is required. Here, we used reverse genetics to develop an FCV reporter virus, inserting NanoLuc luciferase into the LC protein of FCV-Urbana (FCV-UrbanaNL). We characterised the replication kinetics of FCV-UrbanaNL in comparison to its parent virus and assessed the stability of the reporter over multiple passages. Subsequently, we developed virus neutralisation assays to assess a range of monoclonal antibodies that recognise FCV Urbana. We then assessed the breadth of neutralisation by exchanging the major capsid protein, VP1, of FCV Urbana with VP1 from the vaccine strain F9 and the VS-FCV strain NSW-E1. Finally, we evaluated the utility of the FCVNL reporter system to screen candidate antiviral compounds, identifying GS-441524 (the active metabolite of the parent nucleoside remdesivir) as having therapeutic potential against FCV. These findings highlight the potential of this reporter virus as a powerful molecular tool to accelerate the discovery and development of novel therapeutics.

microbiology↗

bioRxiv2022

Rising SARS-CoV-2 Seroprevalence and Patterns of Cross-Variant Antibody Neutralization in UK Domestic Cats

Recent evidence confirming cat-to-human SARS-CoV-2 transmission has highlighted the importance of monitoring infection in domestic cats. Although the effects of SARS-CoV-2 infection on feline health are poorly characterized, cats have close contact with humans, and with both domesticated and wild animals. Accordingly, they could act as a reservoir of infection, an intermediate host and a source of novel variants. To investigate the spread of the virus in the cat population, serum samples were tested for SARS-CoV-2 antibodies by ELISA and a pseudotype-based virus neutralization assay, designed to detect exposure to variants known to be circulating in the human population. Overall seroprevalence was 3.2%, peaking at 5.3% in autumn 2021. Variant-specific neutralizing antibody responses were detected with titers waning over time. The variant-specific response in the feline population correlated with and trailed the variants circulating in the human population, indicating multiple ongoing human-to-cat spill-over events.

immunology↗

bioRxiv2020

Respiratory disease in cats associated with human-to-cat transmission of SARS-CoV-2 in the UK

Two cats from different COVID-19-infected households in the UK were found to be infected with SARS-CoV-2 from humans, demonstrated by immunofluorescence, in situ hybridisation, reverse transcriptase quantitative PCR and viral genome sequencing. Lung tissue collected post-mortem from cat 1 displayed pathological and histological findings consistent with viral pneumonia and tested positive for SARS-CoV-2 antigens and RNA. SARS-CoV-2 RNA was detected in an oropharyngeal swab collected from cat 2 that presented with rhinitis and conjunctivitis. High throughput sequencing of the virus from cat 2 revealed that the feline viral genome contained five single nucleotide polymorphisms (SNPs) compared to the nearest UK human SARS-CoV-2 sequence. An analysis of cat 2s viral genome together with nine other feline-derived SARS-CoV-2 sequences from around the world revealed no shared catspecific mutations. These findings indicate that human-to-cat transmission of SARS-CoV-2 occurred during the COVID-19 pandemic in the UK, with the infected cats developing mild or severe respiratory disease. Given the versatility of the new coronavirus, it will be important to monitor for human-to-cat, cat-to-cat and cat-to-human transmission.

microbiology↗

bioRxiv2017

T cell activation and the HLA locus associate with latent infections of human African trypanosomiasis

Infections by many pathogens can result in a wide range of phenotypes, from severe to mild, or even asymptomatic. Understanding the genetic basis of these phenotypes can lead to better tools to treat patients or detect reservoirs. To identify human genetic factors that contribute to symptoms diversity, we examined the range of disease severities caused by the parasite T. b. gambiense, the primary cause of human African trypanosomiasis (HAT). We analyzed the transcriptomes of immune cells from both symptomatic HAT cases and individuals with latent infections. Our analysis identified several genes and pathways that associated with the latent phenotype, primarily suggesting increased T and B cell activation in HAT patients relative to latent infections. We also used these transcriptome data to conduct an exome-wide single nucleotide polymorphism (SNP) association study. This suggested that SNPs in the human major histocompatibility locus (HLA) associate with severity, supporting the transcription data and suggesting that T cell activation is a determining factor in outcome. Finally, to establish if T cell activation controls disease severity, we blocked co-stimulatory dependent T cell activation in an animal model for HAT. This showed that reducing T cell activation during trypanosome infection improves symptoms and reduces parasitemia. Our data has used a combination of transcriptome-wide analysis and an in vivo model to reveal that T cell activation and the HLA locus associate with the development of symptoms during HAT. This may open new avenues for the development of new therapeutics and prognostics.

genetics↗