Biology subjects

Gamble, A.

Publications and source records attributed to Gamble, A..

15 recordsLinked to original sources

bioRxiv2026

Genomes of Betacoronavirus gravedinis from white-footed mice in New York City and a phylogenetically weighted model of its probable distribution in North America

Rodents are an important reservoir of zoonotic viruses and are ubiquitously present in densely populated urban areas. Betacoronaviruses in the Embecovirus lineage are well known to infect both humans and animals and have established rodent reservoirs. Here three Betacoronavirus gravedinis genomes were sequenced and characterized in white footed mice (Peromyscus leucopus, commonly white footed mice) collected in New York City, the second most populous city in North America. The genomes were distinct from mouse hepatitis virus (MHV), the prototype mouse betacoronavirus, and highly similar and identical in one case to previously characterized B. gravedinis sequences from white footed mice in Connecticut. Codon aware evolutionary models were used to identify specific sites under positive selection within the spike protein of B. gravedinis. A novel method was developed to predict the probable geographic distribution of the virus using publicly available data from the Global Biodiversity Information Facility to generate a weighted distribution map highlighting overlapping potential host ranges based on the evolutionary distance using a high resolution cytocrome B (CYTB) phylogeny of rodent species with potentially overlapping ranges. Our models predict three current hotspots of circulation in North America under different possible transmission regimes, and an additional fourth hotspot was predicted to arise in a warming future. This study highlights the continued need for biodiversity-informed surveillance of potential zoonotic pathogens in rodents.

microbiology↗

bioRxiv2026

Drivers of host-infectious agent community associations in seabirds from sub-Antarctic oceanic islands

Understanding the patterns and drivers of infectious disease dynamics at different levels of life organization is a fundamental disease ecology challenge. In this study, we performed a multi-infectious agents (IA) screening of 1,983 individuals belonging to 18 seabird species, sampled between 2017 and 2022 across five sub-Antarctic islands in the Southern Indian and Atlantic Oceans. Our aim was to identify the drivers of IA community in these seabirds by considering intrinsic and extrinsic factors on three dimensions: distance between seabird metapopulations and within-island sites, macro-community (host functional traits based on feeding and breeding features) and intra-host IA community composition. Samples were screened for 24 DNA-based IAs using a high-throughput real-time PCR method, followed by subsequent hierarchical modelling of species communities. Campylobacter lari, Escherichia coli, Pasteurella multocida, Chlamydiaceae and Mycobacterium spp. were found to be present on all islands in some, but not all, species. However, only E. coli was detected in all species. According to our modelling results, the influence of year and within-island site had limited influence on IA presence/absence, accounting respectively for an average of 1.0% and 1.8% of the variation in IA community. Including host species as a response variable produced a better model fit than including host species functional traits, highlighting the difficulty in simplifying systems by focusing on high-level functional categories. Model outputs show how each species influences IA distribution depending on IA traits, but no clear trend has emerged. Interestingly, burrowing species were less frequently infected with directly transmitted IAs, probably due to the low frequency of transmission events associated with their breeding features and limited social contacts. Our findings pave the way for further multi-dimension studies that would combine complementary approaches to disentangle the complex processes at play in the dynamics of hosts and IAs interactions.

ecology↗

bioRxiv2026

High pathogenicity avian influenza virus H5N1 clade 2.3.4.4b in Antarctica: Multiple Introductions and the First Confirmed Infection of Ice-Dependent Seals

Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b has expanded rapidly across the Southern Ocean since 2023, causing extensive mortality in sub-Antarctic wildlife. Yet its penetration into Antarctica and impacts on ice-dependent species remain poorly resolved primarily due to surveillance constraints. We report the first confirmed H5N1 infection in an Antarctic ice-dependent seal (crabeater seal; Lobodon carcinophaga) and document mortality of crabeater seals across the northern Weddell Sea during November-December 2024. Combining genomic, serological and observational data across nine species, we detected H5N1 RNA in a crabeater seal and a kelp gull (Larus dominicanus), and recovered complete HA, NA and M2 gene sequences from both. Phylogenetic analyses allowed us to identify at least two independent introductions of HPAI H5N1 clade 2.3.4.4b into the northern Antarctic Peninsula region. Serology provided strong evidence of prior exposure in scavenging birds, but no detectable H5 immunity in penguins or pinnipeds. Together, the results demonstrate ongoing novel viral incursions into Antarctica, likely facilitated by at-sea processes e.g. animal interactions on ice floes, that remain invisible to land-based surveillance. These findings highlight the vulnerability of ice-dependent pinnipeds to HPAI H5N1 clade 2.3.4.4b and the urgent need for expanded integrated Antarctic monitoring frameworks that pair serology, opportunistic carcass sampling and genomic sequencing.

ecology↗

bioRxiv2025

A nuclease-driven mechanism of post-replicative ssDNA gap suppression.

During replication stress, failure to resolve post-replicative ssDNA gaps generated by PRIMPOL-mediated replication repriming is linked with chemosensitivity, and in all models reported to date the nuclease MRE11 has been implicated as a gap-promoting factor. We have dissected ssDNA gap dynamics following nucleoside analogue-mediated nascent strand termination and report a novel mechanism via which loss of the MRE11 negative regulator MRN-Interacting Protein (MRNIP) leads to MRE11 exonuclease-dependent suppression of post-replicative ssDNA gaps. This process is driven by UBC13 and the B-family TLS polymerase REV3L, suggesting that in the absence of MRNIP, dysregulated MRE11 activity at chain termination sites licenses gap filling via template switching. In the absence of PRIMPOL-dependent repriming, MRNIP loss leads to paradoxical SMARCAL1, MRE11 and primosome-dependent ssDNA gaps, suggesting that nucleolytic digestion of reversed forks generates DNA intermediates that platform primase redundancy in the context of chain termination. We also highlight novel site-specific roles for the anti-resection factor 53BP1 in enabling primase redundancy via suppression of the nuclease EXO1, and in limiting the EXO1-dependent processing of post-replicative ssDNA gaps. Finally, we demonstrate that CDK-dependent MRNIP phosphorylation is required for MRNIP functionality in the regulation of ssDNA gaps and sensitivity to chain terminators. This work represents the first report of nuclease-driven post-replicative gap filling, illuminates an additional level of versatility in the replication stress response, and expands our understanding of the context-dependent links between nuclease regulation and chemoresistance.

cancer biology↗

bioRxiv2025

Machine Learning Enables Viral Genome-Agnostic Classification of RNA Virus Infections from Host Transcriptomes

Targeted PCR diagnosis of RNA viruses is sequence dependent, meaning that the accuracy of the assay depends on the identity of the viral sequence. However, sequence-targeted assays can miss novel or divergent viruses. We test whether the host transcriptome alone can classify RNA virus infections without using viral sequences. Using publicly available data on Huh7 and Calu-3 cells experimentally infected with diverse negative-sense RNA, we evaluate two host-derived feature sets (differential expression dataset of identified genes and alignment-free nucleotide k-mer spectra) and compare hierarchical clustering with Random Forests. Across datasets and timepoints (12 to 24 hpi), Random forests accurately distinguished cells infected with different viruses. Controls with label permutation and read shuffling across experimental conditions established non-random performance. Influenza A infections exhibited the strongest, most distinct signatures, whereas Ebola and Lassa virus responses were subtler yet still classifiable. These results show that host-only transcriptomics encodes virus-specific, complex signals that machine learning can exploit, enabling genome-agnostic classification of infection statuses. This approach could aid early outbreak triage when primer based detection methods fail or viral genomes are unknown and complements sequence-based discovery.

microbiology↗

bioRxiv2025

IFI16 senses and protects stalled replication forks

Replication stress is a key driver of DNA damage and genome instability. Replication stress-induced fork remodelling generates a new DNA end that is vulnerable to the action of nucleases, and which is protected by a range of factors including the canonical tumour suppressors BRCA1 and BRCA2. Here we report that replication stress drives elevated production of cytokines and chemokines in the absence of DNA damage. The DNA sensor IFI16 binds nascent DNA at stalled replication forks and signals via the DNA sensing adaptor STING, to induce the activation of NF-{kappa}B and the production of pro-inflammatory cytokines in response to replication stress. IFI16 also acts directly at stalled replication forks to protect nascent DNA from degradation by the nucleases MRE11 and DNA2. Furthermore, IFI16 is required for the interferon-mediated rescue of fork protection in BRCA-deficient cells, highlighting the critical role of IFI16 in the cross-talk between innate immunity and fork protection during replication stress. HighlightsO_LIReplication stress induces an early innate immune response, which is dependent on the DNA sensing factors IFI16 and STING, but not cGAS C_LIO_LIIFI16 binds directly to nascent DNA at stalled replication forks C_LIO_LIIFI16 prevents nucleolytic degradation of reversed forks C_LIO_LIIFI16 is required for interferon-mediated fork protection in BRCA-deficient cells C_LI

cancer biology↗

bioRxiv2023

Connectivity of marine predators over the Patagonian Shelf during the highly pathogenic avian influenza (HPAI) outbreak

Animal movement and population connectivity are key areas of uncertainty in efforts to understand and predict the spread of infectious disease. The emergence of highly pathogenic avian influenza (HPAI) in South America poses a significant threat to globally significant populations of colonial breeding marine predators in the South Atlantic. Yet, there is a poor understanding of which species or migratory pathways may facilitate disease spread. Compiling one of the largest available animal tracking datasets in the South Atlantic, we examine connectivity and inter-population mixing for colonial breeding marine predators tagged at the Falkland Islands. We reveal extensive connectivity for three regionally dominant and gregarious species over the Patagonian Shelf. Black browed albatrosses (BBA), South American fur seals (SAFS) and Magellanic penguins (MAG) used coastal waters along the Atlantic coast of South America (Argentina and Uruguay). These behaviours were recorded at or in close proximity to breeding colonies and haul-out areas with dense aggregations of marine predators. Transit times to and from the Falkland Islands to the continental coast ranged from 0.2 - 70 days, with 84% of animals making this transit within 4 days - a conservative estimate for HPAI infectious period. Our findings show the incursion of HPAI to the Falkland Islands marine predator community is a highly credible threat, which may be facilitated by BBA, SAFS and MAG connectivity with South America. This information is vital in supporting HPAI disease surveillance, risk assessment and marine management efforts across the region. SignificanceThe recent emergence of highly pathogenic avian influenza (HPAI) in South America poses a major threat to globally significant marine predator populations in the South Atlantic. There is extensive connectivity over the southern Patagonian Shelf between regionally dominant seal and seabird populations, with potential for large-scale pathogen spread. Despite this connectivity, outbreaks of HPAI are unevenly distributed across the region. Connectivity information is integral for regional disease surveillance, predictive modelling and population viability assessments.

ecology↗

bioRxiv2023

No evidence for highly pathogenic avian influenza virus H5N1 (clade 2.3.4.4b) in the Antarctic region during the austral summer 2022/23

The current highly pathogenic avian influenza H5N1 panzootic has substantial impacts on wild birds and marine mammals. Although major outbreaks occurred in South America, incursion to Antarctica emerged late in the breeding season of 2023/2024 and was confined the wider region of the Antarctic Peninsula. To infer potential underlying processes, we compiled H5N1 surveillance from Antarctica and Sub-Antarctic Islands prior to the first confirmed cases.

microbiology↗

bioRxiv2023

Strong breeding colony fidelity in northern gannets following High Pathogenicity Avian Influenza Virus (HPAIV) outbreak

High pathogenicity avian influenza virus (HPAIV) caused the worst seabird mass-mortalities on record in Europe across 2021-2022. The northern gannet (Morus bassanus) was one of the most affected species, with tens of thousands of casualties in the northeast Atlantic between April-September 2022. Disease outbreaks can drastically modify the movement ecology of animals and diminish spatial consistency, thereby increasing the potential for disease transmission. To detect potential changes in movement behaviour, we GPS-tracked breeding adults following the initial HPAIV outbreak, at three of the largest gannet breeding colonies where major mortality of adults and chicks occurred (Bass Rock, Scotland, UK; Grassholm, Wales, UK; Rouzic island, Brittany, France). Crucially, GPS-tracked birds remained faithful to their breeding sites and did not prospect other breeding colonies. They performed regular foraging trips at sea, similar to their behaviour before the outbreak. Gannet foraging effort was nonetheless lower than in 2019, thus surviving birds may have benefited from reduced intra- and interspecific food competition. Breeding colony fidelity of adult northern gannets following HPAIV mass-mortalities suggests limited long-term capacity to virus spread, which may contrast with the behaviour of adults during the disease outbreak, or with that of younger individuals.

ecology↗

bioRxiv2022

Comparative aerosol and surface stability of SARS-CoV-2 Variants of Concern

SARS-CoV-2 is transmitted principally via air; contact and fomite transmission may also occur. Variants-of-concern (VOCs) are more transmissible than ancestral SARS-CoV-2. We find that early VOCs show greater aerosol and surface stability than the early WA1 strain, but Delta and Omicron do not. Stability changes do not explain increased transmissibility.

microbiology↗

bioRxiv2022

Climate change in the Arctic: testing the poleward expansion of ticks and tick-borne diseases

Climate change is most strongly felt in the polar regions of the world, with significant impacts for the species that live in these extreme environments. The arrival of parasites and pathogens from more temperate areas may become a significant problem for these populations, but current observations of parasite presence often lack a historical reference of prior absence. Observations in the high Arctic of the seabird tick Ixodes uriae suggested that this species recently expanded its range poleward. As this tick can have a direct impact on the breeding success of its seabird hosts and is vector of many potential disease agents, including Lyme disease spirochaetes, its presence and origin are important elements for predicting its impact on polar seabird populations. Here, we use population genetic data and host serology to test the hypothesis that Ixodes uriae has recently expanded into the Svalbard archipelago. Both Black-legged kittiwakes (Rissa tridactyla) and Thick-billed murres (Uria lomvia) were captured in Kongsfjorden, Spitsbergen and sampled for ticks and blood. Collected ticks were genotyped using microsatellite markers and population genetic analyses were carried out using data from 14 additional seabird colonies distributed across the ticks northern distribution. In contrast to predictions based on a recent expansion, the Spitsbergen population showed high genetic diversity and significant differentiation from the more southern populations, suggesting long-term population isolation. Host serology also demonstrated a high exposure rate to Lyme disease spirochaetes (Bbsl). Targeted PCR on tick DNA extracts and sequencing identified the presence of Borrelia garinii in a Spitsbergen tick, confirming seabird exposure and demonstrating the presence of Lyme disease bacteria in the high Arctic for the first time. Taken together, results contradict the notion that Ixodes uriae has recently expanded into the high Arctic region. Rather, this tick has likely been present for some time, maintaining relatively high population sizes and an endemic transmission cycle of Bbsl spirochaetes. Close future observations of population infestation/infection rates will now be necessary to relate epidemiological changes to ongoing climate modifications. Author summaryThe climate in the Arctic is rapidly changing, and with it, the flora and fauna that live there. These new environmental conditions can favor the establishment of invasive species, including novel parasites and pathogens. Here, we use population genetic data and host serology to examine whether recent observations of ticks infesting breeding seabirds in the high Arctic represent a poleward expansion of the parasite. Contrary to predictions, tick populations showed no evidence of a recent colonization of the region. Ticks have likely be present for a relatively long time, maintaining high local diversity despite harsh environmental conditions and vectoring infectious agents among breeding birds. Indeed, we demonstrate the presence of Lyme disease spirochaetes in the high Arctic for the first time, with bacterial DNA found in one of the sampled ticks and seabird serology demonstrating high exposure to this pathogen. This Lyme disease agent has therefore likely been established in the region and circulating at low frequency between seabirds and ticks for some time.

ecology↗

bioRxiv2022

Genomic characterisation of a novel species of Erysipelothrix associated with mortalities among endangered seabirds

Infectious diseases threaten endangered species, particularly in small isolated populations. Seabird populations on the remote Amsterdam Island in the Indian Ocean have been in decline for the past three decades, with avian cholera caused by Pasteurella multocida proposed as the primary driver. However, Erysipelothrix spp. has also been sporadically detected from albatrosses on Amsterdam Island and may be contributing to some of the observed mortality. In this study, we genomically characterised 16 Erysipelothrix spp. isolates obtained from three Indian yellow-nosed albatross chick carcasses in 2019. Two isolates were sequenced using both Illumina short-read and MinION long-read approaches, which - following hybrid assembly - resulted in closed circular genomes. Mapping of Illumina reads from the remaining isolates to one of these new reference genomes revealed that all 16 isolates were closely related, with a maximum of 13 nucleotide differences distinguishing any pair of isolates. The nucleotide diversity of isolates obtained from the same or different carcasses was similar, suggesting all three chicks were likely infected from a common source. These genomes were compared with a global collection of genomes from E. rhusiopathiae and other species from the same genus. The isolates from albatrosses were phylogenetically distinct, sharing a most recent common ancestor with E. rhusiopathiae. Based on phylogenomic analysis and standard thresholds for average nucleotide identity and digital DNA-DNA hybridisation, these isolates represent a novel Erysipelothrix species, for which we propose the name Erysipelothrix amsterdamensis sp. nov. The type strain is E. amsterdamensis A18Y020dT. The implications of this bacterium for albatross conservation will require further study.

genomics↗

bioRxiv2020

The effect of temperature and humidity on the stability of SARS-CoV-2 and other enveloped viruses

Environmental conditions affect virus inactivation rate and transmission potential. Understanding those effects is critical for anticipating and mitigating epidemic spread. Ambient temperature and humidity strongly affect the inactivation rate of enveloped viruses, but a mechanistic, quantitative theory of those effects has been elusive. We measure the stability of the enveloped respiratory virus SARS-CoV-2 on an inert surface at nine temperature and humidity conditions and develop a mechanistic model to explain and predict how temperature and humidity alter virus inactivation. We find SARS-CoV-2 survives longest at low temperatures and extreme relative humidities; median estimated virus half-life is over 24 hours at 10 {degrees}C and 40 % RH, but approximately 1.5 hours at 27 {degrees}C and 65 % RH. Our mechanistic model uses simple chemistry to explain the increase in virus inactivation rate with increased temperature and the U-shaped dependence of inactivation rate on relative humidity. The model accurately predicts quantitative measurements from existing studies of five different human coronaviruses (including SARS-CoV-2), suggesting that shared mechanisms may determine environmental stability for many enveloped viruses. Our results indicate scenarios of particular transmission risk, point to pandemic mitigation strategies, and open new frontiers in the mechanistic study of virus transmission.

microbiology↗

bioRxiv2020

Heat-treated virus inactivation rate depends strongly on treatment procedure

Decontamination helps limit environmental transmission of infectious agents. It is required for the safe re-use of contaminated medical, laboratory and personal protective equipment, and for the safe handling of biological samples. Heat treatment is a common decontamination method, notably used for viruses. We show that for liquid specimens (here, solution of SARS-CoV-2 in cell culture medium), virus inactivation rate under heat treatment at 70{degrees}C can vary by almost two orders of magnitude depending on the treatment procedure, from a half-life of 0.86 min (95% credible interval: [0.09, 1.77]) in closed vials in a heat block to 37.00 min ([12.65, 869.82]) in uncovered plates in a dry oven. These findings suggest a critical role of evaporation in virus inactivation via dry heat. Placing samples in open or uncovered containers may dramatically reduce the speed and efficacy of heat treatment for virus inactivation. Given these findings, we reviewed the literature temperature-dependent coronavirus stability and found that specimen containers, and whether they are closed, covered, or uncovered, are rarely reported in the scientific literature. Heat-treatment procedures must be fully specified when reporting experimental studies to facilitate result interpretation and reproducibility, and must be carefully considered when developing decontamination guidelines. ImportanceHeat is a powerful weapon against most infectious agents. It is widely used for decontamination of medical, laboratory and personal protective equipment, and for biological samples. There are many methods of heat treatment, and methodological details can affect speed and efficacy of decontamination. We applied four different heat-treatment procedures to liquid specimens containing SARS-CoV-2. Our results show that the container used to store specimens during decontamination can substantially affect inactivation rate: for a given initial level of contamination, decontamination time can vary from a few minutes in closed vials to several hours in uncovered plates. Reviewing the literature, we found that container choices and heat treatment methods are only rarely reported explicitly in methods sections. Our study shows that careful consideration of heat-treatment procedure -- in particular the choice of specimen container, and whether it is covered -- can make results more consistent across studies, improve decontamination practice, and provide insight into the mechanisms of virus inactivation.

microbiology↗

bioRxiv2019

Exploring the infection dynamics of a bacterial pathogen on a remote oceanic island reveals annual epizootics impacting an albatross population

Oceanic islands with reduced species richness provide an opportunity to investigate the emergence, maintenance and transmission of infectious diseases threatening wildlife. On Amsterdam Island, in the southern Indian Ocean, massive and recurrent mortality of the nestlings of Indian yellow-nosed albatross (Thalassarche carteri) has been attributed to avian cholera caused by Pasteurella multocida, a bacterial pathogen of likely human introduction. To understand the annual dynamics of pathogen prevalence, we measured the shedding of bacterial DNA by the albatrosses during four successive breeding seasons. The screening of 583 bird swabs by Real-Time PCR revealed an intense circulation of P. multocida during each study year, with a steady increase of infection prevalence across the breeding season. In the three years of highest pathogen prevalence, the epizootics were associated with massive die-offs of nestlings, inducing low annual fledging success (< 20%). These findings and developed PCR protocol have crucial applications for refining wildlife conservation plans aiming at controlling this disease.

ecology↗