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Bamford, C. G. G.

Publications and source records attributed to Bamford, C. G. G..

12 recordsLinked to original sources

Spatio-temporal machine learning for multi-horizon prediction of bluetongue outbreaks

Reliable early warning of infectious disease outbreaks remains a major challenge for surveillance systems, particularly for vector-borne pathogens whose transmission depends on interactions among hosts, vectors, and climate-sensitive environmental conditions. Data-driven forecasting offers a promising approach for predicting outbreak risk using surveillance and environmental data. This study develops a logit-weighted ensemble (LWE), a machine-learning framework that predicts outbreak occurrence 1-6 months ahead at the administrative unit-month scale using routinely available outbreak notifications and gridded climate data. Bluetongue virus (BTV), an arbovirus of ruminants transmitted by Culicoides biting midges, provides a well-characterised system in which transmission is strongly shaped by climate, making it a useful system for applying and testing this approach. The framework is evaluated using surveillance data collected between 2005 and 2024 from France, Greece, and Italy, selected for their long-running and high-quality outbreak surveillance records. Across all three countries, the LWE achieved the strongest and most stable predictive performance under a recall-focused evaluation that prioritises correctly identifying outbreak months. It outperformed or matched 14 benchmark models, with differences becoming more pronounced at longer lead times (month +3 onward), when predictions are more uncertain and outbreaks are relatively rare. Predictability varied across countries, with the highest performance in Greece, strong performance in France, and lower, more variable performance in Italy, reflecting differences in how consistently outbreaks occur and spread across regions. Overall, the results demonstrate that horizon-aware, climate-informed forecasting can reliably identify months and locations at elevated risk of outbreak occurrence up to six months in advance, supporting surveillance planning and preparedness across heterogeneous European settings. The ensemble framework provides a robust and portable strategy for outbreak prediction using routinely collected surveillance and environmental data. Author SummaryPredicting infectious disease outbreaks before they occur remains a major challenge, particularly for diseases influenced by environmental conditions. In this study, we focus on bluetongue, a viral disease of livestock transmitted by biting midges, where transmission is strongly affected by climate and seasonal patterns. We develop a method that uses routinely collected outbreak reports and climate data to estimate where and when outbreaks are more likely to occur, up to six months in advance. We apply this approach across three European countries with a history of bluetongue outbreaks. We find that combining climate information with recent outbreak patterns can provide useful early signals of increased risk. Predictions are most accurate at shorter timeframes, but longer-range forecasts can still support planning and preparedness. Because our approach uses widely available data, it could be applied in other regions or to similar environmentally driven diseases. However, it does not include factors such as vaccination, animal movement, or detailed information on vector populations, which may also influence how outbreaks develop. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=98 SRC="FIGDIR/small/726753v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@45e41borg.highwire.dtl.DTLVardef@82c787org.highwire.dtl.DTLVardef@1f97888org.highwire.dtl.DTLVardef@1586747_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

Substantial cold tolerance in all life stages of the biting midge Culicoides nubeculosus (Diptera: Ceratopogonidae)

In temperate regions, vector-borne disease risk is mediated by cold winter conditions, however, the cold tolerance of key vector taxa remains poorly understood. Culicoides biting midges are the primary vectors of several pathogens of medical and veterinary importance including bluetongue virus, where seasonal cold weather in temperate regions limits midge activity and pathogen transmission. Here, we provide the first comprehensive assessment of cold tolerance across all developmental stages of Culicoides nubeculosus, a widely used laboratory species that is endemic to northern Europe. Eggs, first-instar larvae, fourth-instar larvae, pupae, and adults were exposed to acute (1 h) and extended (6 and 24 h) cold treatments spanning -1 to -18 {degrees}C, with survival, development, emergence, and adult wing size quantified. Culicoides nubeculosus showed substantial but stage-specific cold tolerance, with survival limits of [≤] -18 {degrees}C for eggs, -14 {degrees}C for pupae, -10 {degrees}C for L1 larvae and adults, and -7 {degrees}C for L4 larvae. While the effect of cold exposure duration varied across temperatures and life stages, extended exposure generally reduced survival at lower temperatures. Cold stress caused sublethal effects, including reduced adult emergence when eggs or larvae were exposed and reductions in adult wing size of up to [~]10%, depending on the life stage. These results reveal substantial cold tolerance across the full life history of C. nubeculosus, suggesting that factors beyond temperature influence population phenology. Our findings provide new insights into Culicoides ecology, with implications for seasonal vector population dynamics and arbovirus transmission risk in temperate regions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/692099v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@199de25org.highwire.dtl.DTLVardef@c75202org.highwire.dtl.DTLVardef@1d91e6dorg.highwire.dtl.DTLVardef@15c9984_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

Age-dependent expression and antiviral activity of interferon epsilon in respiratory epithelium

Respiratory syncytial virus (RSV) disease burden is greatest between six weeks and 6 months of life, with young age the most common risk factor among hospitalised children. A robust innate immune response in the airway epithelium is crucial for mitigating RSV-associated disease, but early-life immune responses to infection remain largely unexplored. RNA-seq analysis of RSV-infected primary nasal epithelial cell cultures from healthy infants at birth and one year revealed diminished expression of interferon epsilon (IFNE), a poorly characterised type I IFN, in newborns versus one-year. We hypothesised, therefore, that IFNE plays an important role during infant RSV infection. We found that IFNE is endogenously expressed in airway epithelial cell lines. Recombinant human IFN{varepsilon} (rhIFN{varepsilon}) induced an antiviral state against an RSV clinical isolate and related Sendai virus, but not SARS-CoV-2 under the conditions tested. The antiviral potency of rhIFN{varepsilon} was diminished relative to rhIFN beta (rhIFN{beta}1) or rhIFN lambda-1 (rhIFN{lambda}1), as evidenced by IC50 data. Importantly, rhIFN{varepsilon} induced similar ISGs as rhIFN{beta}1 but demonstrated a transient temporal expression profile that differed from both rhIFN{beta}1 and rhIFN{lambda}1. These results suggest that lower IFN{varepsilon} expression at birth may contribute to increased susceptibility to severe RSV-associated disease, offering insights into potential therapeutic interventions.

microbiology↗

Long Term Virucidal Activity of Rosin Soap on Surfaces

Microbiocidal products for decontaminating both animate and inanimate surfaces that may act as vectors for disease transmission are a well-established method for inactivating viruses of clinical significance. There are a wide variety of such microbiocidal products that can be purchased commercially, many with different active ingredients. We have recently shown that Rosin soap (derived from Tall Oil that has been produced by trees) is a highly effective virucidal product against enveloped viruses like influenza A virus and SARS-CoV-2 when tested in solution. Here we further demonstrate that Rosin soap retains its virucidal activity against influenza A virus and SARS-CoV-2 when applied to surfaces, such as plastic, glass and steel, either before or after virus inoculation. The virucidal activity extended out to seven days post administration. Together, our results show the potential for Rosin soap-based disinfectants to be used as a surface coating to protect against clinically relevant enveloped viruses, such as influenza viruses and coronaviruses.

microbiology↗

Comparative analysis of genome-encoded viral sequences reveals the evolutionary history of Flaviviridae.

The flavivirids (family Flaviviridae) are a group of positive-strand RNA viruses that pose serious risks to human and animal health on a global scale. Here we use flavivirid-derived DNA sequences, identified in animal genomes, to reconstruct the long-term evolutionary history of family Flaviviridae. We demonstrate that flavivirids are >100 million years old and show that this timing can be combined with dates inferred from co-phyletic analysis to produce a cohesive overview of their evolution, distribution and diversity wherein the main flavivirid subgroups originate in early animals and broadly co-diverge with major animal phyla. In addition, we reveal evidence that the classical flaviviruses of vertebrates, most of which are transmitted via blood-feeding arthropod vectors, originally evolved in hematophagous arachnids and later acquired the capacity to be transmitted by insects. Our findings imply that the biological properties of flavivirids have been acquired gradually over the course of animal evolution. Thus, broad-scale comparative analysis will likely reveal fundamental insights into their biology. We therefore published our results via an open, extensible, database (Flavivirid-GLUE), which we constructed to facilitate the wider utilisation of genomic data and evolution-related domain knowledge in flavivirid research.

evolutionary biology↗

An Endogenously activated antiviral state restricts SARS-CoV-2 infection in differentiated primary airway epithelial cells

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the coronavirus disease-19 (COVID-19) pandemic, was identified in late 2019 and went on to cause over 3.3 million deaths in 15 months. To date, targeted antiviral interventions against COVID-19 are limited. The spectrum of SARS-CoV-2 infection ranges from asymptomatic to fatal disease. However, the reasons for varying outcomes to SARS-CoV-2 infection are yet to be elucidated. Here we show that an endogenously activated interferon lambda (IFN{lambda}) pathway leads to resistance against SARS-CoV-2 infection. Using a well-differentiated primary nasal epithelial cell (WD-PNEC) model from multiple adult donors, we discovered that susceptibility to SARS-CoV-2 infection, but not respiratory syncytial virus (RSV) infection, varied. One of four donors was resistant to SARS-CoV-2 infection. High baseline IFN{lambda} expression levels and associated interferon stimulated genes correlated with resistance to SARS-CoV-2 infection. Inhibition of the JAK/STAT pathway in WD-PNECs with high endogenous IFN{lambda} secretion resulted in higher SARS-CoV-2 titres. Conversely, prophylactic IFN{lambda} treatment of WD-PNECs susceptible to infection resulted in reduced viral titres. An endogenously activated IFN{lambda} response, possibly due to genetic differences, may be one explanation for the differences in susceptibility to SARS-CoV-2 infection in humans. Importantly, our work supports the continued exploration of IFN{lambda} as a potential pharmaceutical against SARS-CoV-2 infection.

immunology↗

Rosin Soap Exhibits Virucidal Activity

Chemical methods of virus inactivation are used routinely to prevent viral transmission in both a personal hygiene capacity but also in at-risk environments like hospitals. Several virucidal products exist, including hand soaps, gels and surface disinfectants. Resin acids, which can be derived from Tall oil produced from trees, have been shown to exhibit anti-bacterial activity. However, whether these products or their derivatives have virucidal activity is unknown. Here, we assessed the capacity of Rosin soap to inactivate a panel of pathogenic mammalian viruses in vitro. We show that Rosin soap can inactivate the human enveloped viruses: influenza A virus (IAV), respiratory syncytial virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For IAV, rosin soap could provide a 100,000-fold reduction in infectivity. However, Rosin soap failed to affect the non-enveloped encephalomyocarditis virus (EMCV). The inhibitory effect of Rosin soap against IAV infectivity was dependent on its concentration but not dependent on incubation time nor temperature. Together, we demonstrate a novel chemical inactivation method against enveloped viruses, which could be of use in preventing virus infections in certain settings. ImportanceViruses remain a significant cause of human disease and death, most notably illustrated through the current Covid-19 pandemic. Control of virus infection continues to pose a significant global health challenge to the human population. Viruses can spread through multiple routes, including via environmental and surface contamination where viruses can remain infectious for days. Methods to inactivate viruses on such surfaces may help mitigate infection. Here we present evidence identifying a novel virucidal product in Rosin soap, which is produced from Tall oil from coniferous trees. Rosin soap was able to rapidly and potently inactivate influenza virus and other enveloped viruses.

microbiology↗

Collaboration Between Host and Viral Factors Shape SARS-CoV-2 Evolution

SARS-CoV-2 continues to evolve, resulting in several variants of concern with novel properties. The factors driving SARS-CoV-2 fitness and evolution in the human respiratory tract remain poorly defined. Here, we provide evidence that both viral and host factors co-operate to shape SARS-CoV-2 genotypic and phenotypic change. Through viral whole-genome sequencing, we explored the evolution of two clinical isolates of SARS-CoV-2 during passage in unmodified Vero-derived cell lines and in parallel, in well-differentiated primary nasal epithelial cell (WD-PNEC) cultures. We identify a consistent, rich genetic diversity arising in vitro, variants of which could rapidly rise to near-fixation with 2 passages. Within isolates, SARS-CoV-2 evolution was dependent on host cells, with Vero-derived cells facilitating more profound genetic changes. However, most mutations were not shared between strains. Furthermore, comparison of both Vero-grown isolates on WD-PNECs disclosed marked growth attenuation mapping to the loss of the polybasic cleavage site (PBCS) in Spike while the strain with mutations in NSP12 (T293I), Spike (P812R) and a truncation of ORF7a remained viable in WD-PNECs. Our work highlights the significant genetic plasticity of SARS-CoV-2 while uncovering an influential role for collaboration between viral and host cell factors in shaping viral evolution and fitness in human respiratory epithelium.

microbiology↗

An interferon lambda 4-associated variant in the hepatitis C virus RNA polymerase affects viral replication in infected cells

Host IFNL4 haplotype status contributes to the development of chronic hepatitis C virus infection in individuals who are acutely infected with the virus. In silico studies revealed that specific amino acid variants at multiple sites on the HCV polyprotein correlate with functional single nucleotide polymorphisms (SNPs) in the IFNL4 locus. Thus, SNPs at the IFNL4 locus may select variants that influence virus replication and thereby outcome of infection. Here, we examine the most significantly IFNL4-associated amino acid variants that lie in the Lambda (L) 2 loop of the HCV NS5B RNA polymerase. L2 loop variants were introduced into both sub-genomic replicon and full-length infectious clones of HCV and viral replication examined in the presence and absence of exogenous IFN{lambda}4. Our data demonstrate that while mutation of NS5B L2 loop affects replication, individual IFNL4-associated variants have modest but consistent effects on replication both in the presence and absence of IFN{lambda}4. Given the strong genetic association between these variants and IFNL4, these data suggest a nuanced effect of each individual position on viral replication, the combined effect of which might mediate resistance to the effects of IFN{lambda}4.

microbiology↗

Strange Stable Replicators Generated From Mumps Virus cDNA Clones

In reverse genetic experiments we have isolated recombinant mumps viruses (rMuV) based on a recent clinical isolate that carry large numbers of mutations clustered in small parts of their genome and which are not caused by biased hyper-mutation. In two separate experiments we obtained such rMuV: one virus had 19 mutations in the V/P region of the genome; the other, which also contained an extra transcription unit encoding green fluorescent protein (EGFP), had 32 mutations in the N gene. These specific constellations of mutations have not been observed in naturally occurring MuV isolates. The vast majority of the mutations (48/51) are synonymous.\n\nOn passage in Vero cells and human B-LCL cells, a B lymphocyte-like cell Line, these mutations appear stable as no reversal occurs to the original consensus sequences, though mutations in other genes occur and change in frequency during passage. Defective Interfering RNAs accumulate in passage in Vero cells but not in B-LCL cells. Interestingly, in all passaged samples the level of variation in the EGFP gene is the same as in the viral genes, though it is unlikely that this gene is under any functionality constraint. The stability in repeated high multiplicity passage indicates that the constellation of mutations is placing the virus on a fitness peak from which it cannot escape. What mechanism gave rise to these mutant viruses and their stability remain open questions of interest to a wider field than mumps reverse genetics alone.

microbiology↗

Interferon lambda 4 impacts broadly on hepatitis C virus diversity.

Type III interferons (IFN-{lambda}) are part of the innate immune response to hepatitis C virus (HCV) infection however the specific role of IFN-{lambda}4 and the nature of the viral adaption to this pressure have not been defined. Here we use paired genome-wide human and viral genetic data in 485 patients infected with HCV genotype 3a to explore the role of IFN-{lambda}4 on HCV evolution during chronic infection. We show that genetic variations within the host IFNL4 locus have a broad and systematic impact on HCV amino acid diversity. We also demonstrate that this impact is larger in patients producing a more active form of IFN-{lambda}4 protein compared to the less active form. A similar observation was noted for viral load. We conclude that IFN-{lambda}4 protein is a likely causal agent driving widespread HCV amino acid changes and associated with viral load and possibly other clinical and biological outcomes of HCV infection.

genomics↗

A Polymorphic Residue That Attenuates Interferon Lambda 4 Activity in Hominid Lineages

As antimicrobial signalling molecules, type III or lambda interferons (IFN{lambda}s) are critical for defence against infection by diverse pathogens. Counter-intuitively, expression of one member of the family, IFN{lambda}4, is associated with decreased clearance of hepatitis C virus (HCV) in the human population; by contrast, a natural in-frame nucleotide insertion that abrogates IFN{lambda}4 production improves viral clearance. To further understand how genetic variation between and within species affects IFN{lambda}4 function, we screened a panel of extant coding variants of human IFN{lambda}4 and identified three variants that substantially affect antiviral activity (P70S, L79F and K154E). The most notable variant was K154E, which enhanced in vitro activity in a range of antiviral and interferon stimulated gene (ISG) assays. This more active E154 variant of IFN{lambda}4 was found only in African Congo rainforest Pygmy hunter-gatherers. Remarkably, E154 was highly conserved as the ancestral residue in mammalian IFN{lambda}4s yet K154 is the dominant variant throughout evolution of the hominid genus Homo. Compared to chimpanzee IFN{lambda}4, the human orthologue had reduced activity due to amino acid substitution of glutamic acid with lysine at position 154. Meta-analysis of published gene expression data from humans and chimpanzees showed that this difference in activity between K154 and E154 in IFN{lambda}4 is consistent with differences in antiviral gene expression in vivo during HCV infection. Mechanistically, our data suggest that human-specific K154 likely affects IFN{lambda}4 activity by reducing secretion and potency. We postulate that evolution of an IFN{lambda}4 with attenuated activity in humans (K154) likely contributes to distinct host-specific responses to and outcomes of infection, such as HCV.

immunology↗