Biology subjects

Holmes, E. C.

Publications and source records attributed to Holmes, E. C..

At least 37 records · Page 2Linked to original sources

bioRxiv2025

Diverse Viral Pathogens in Australian Canines: Limited Geographic Structure and the First Detection of an RNA Virus in Dingoes

Viruses impose a substantial disease burden on dogs and the close relationship between dogs and humans may facilitate zoonotic disease emergence. Australias geographic isolation, strict biosecurity measures and native dingo populations present a unique model for understanding the spread and evolution of canine viruses. However, aside from a few well-characterised pathogens, genomic data are scarce for many common dog viruses, limiting our understanding of their evolution and disease ecology. Using a metatranscriptomic approach we identified the viruses in dogs and dingoes from various geographical locations across mainland Australia and sample types, revealing 86 vertebrate-associated viruses belonging to 16 distinct species, including a new vesivirus-like species. Many of the viruses identified here have not previously been sequenced in Australia. We identified important dog pathogens associated with canine infectious respiratory disease syndrome--such as canine pneumovirus, canine herpesvirus, and canine respiratory coronavirus--and gastroenteritis, including canine parvovirus, canine coronavirus, and rotavirus A. The sequences of Australian canine viruses often occupied multiple distinct clades phylogenetically and had little geographic structure, suggesting multiple virus introductions and subsequent spread across the country. Notably, we identified the first RNA virus - rotavirus A - in a dingo. This virus was phylogenetically distinct from dog-associated rotavirus A sequences and more closely related to viruses found in humans and bats, indicative of the past cross-species transmission of a reassortant virus into dingoes, and shows dingoes and domestic dogs may have distinct viromes. Our findings expand the knowledge of viral diversity in Australian canines, improving our understanding of viral movement into and within Australia, as well as the potential zoonotic risks associated with dogs and dingoes.

microbiology↗

bioRxiv2025

Infectome Analysis of Small Mammals in Southern China Reveals Ecological Associations and Emerging Threats from Diverse Pathogens

Small mammals harbor a diverse array of zoonotic pathogens. To date, however, metagenomic surveys of these species have primarily focused on viral diversity, with limited attention paid to bacteria and eukaryotic pathogens. Additionally, the ecological determinants of pathogen diversity within these mammals have not been systematically examined. Herein, we employed a metatranscriptomics approach to survey the pathogen infectome of 2,408 individual samples, representing lung, liver, and gut tissues from 858 animals collected throughout Guangdong province, China, with a study design that accounted for host species, tissue, season, and geographic location. We identified 76 pathogen species, including 29 RNA viruses, 12 DNA viruses, 5 bacteria, and 30 eukaryotic pathogens, 33 of which were newly discovered. Tissue distribution analysis revealed distinct organotropisms, suggesting varied transmission routes, while host distribution analysis showed that each animal carried an average of one pathogen, with 10 pathogens widely distributed among mammalian orders. Our characterization of the geographic and seasonal patterns revealed that pathogen richness was primarily influenced by region, host species, and season, while pathogen composition was largely shaped by host genetic distance. Collectively, these data provide the first comprehensive insight into the dynamics of the pathogen infectome in these key mammalian disease reservoirs, highlighting the major factors driving pathogen diversity and transmission.

microbiology↗

bioRxiv2025

Infectome analysis of bat kidneys from Yunnan province, China, reveals close relatives of Hendra-Nipah viruses and prevalent bacterial and eukaryotic pathogens

Bats are natural reservoirs for a wide range of microorganisms, including many notable zoonotic pathogens. However, the infectome of bat kidneys remains poorly understood. To address this gap, we performed meta-transcriptomic sequencing on kidney tissues from 142 bats, spanning ten species sampled at five locations in Yunnan province, China. This analysis identified 22 viral species, including 20 novel viruses, two of which represented newly discovered henipaviruses closely related to the highly pathogenic Hendra and Nipah viruses. These henipaviruses were found in the kidneys of bats inhabiting an orchard near villages, raising concerns about potential fruit contamination via bat urine and transmission risks to livestock or humans. Additionally, we identified a novel protozoan parasite, tentatively named Klossiella yunnanensis, along with two highly abundant bacterial species, one of which is a newly discovered species--Flavobacterium yunnanensis. These findings broaden our understanding of the bat kidney infectome, underscore critical zoonotic threats, and highlight the need for comprehensive, full-spectrum microbial analyses of previously understudied organs to better assess spillover risks from bat populations.

microbiology↗

bioRxiv2025

Comprehensive Infectome Analysis Reveals Diverse Infectious Agents with Zoonotic Potential in Wildlife

Understanding wildlife-pathogen interactions is crucial for mitigating zoonotic risk. Through meta-transcriptomic sequencing we profiled the infectomes of 1,922 samples from 67 mammalian species across China, uncovering a remarkable diversity of viral, bacterial, fungal, and parasitic pathogens. Of the 195 pathogens identified, 62 were novel, including a bi- segmented coronavirus in diseased lesser pandas, which we propose represents a new genus - Zetacoronavirus. The orders Carnivora and Rodentia exhibited the highest pathogen diversity and were implicated in numerous host-jumping events. Comparative analysis of diseased versus healthy animals revealed a trend of higher pathogen loads in the former, with possible differences in tissue tropisms. In total, 48 zoonotic and 17 epizootic pathogens were identified, with frequent cross-species transmission, emphasizing the potential for emerging public health threats. This study highlights the urgent need for wildlife pathogen surveillance to inform proactive disease management strategies.

microbiology↗

bioRxiv2024

Tunicate metatranscriptomes reveal ancient virus-host co-divergence and inter-order recombination in the evolutionary history of disease-causing viruses

Tunicates are a key transitional taxon in animal evolution as the closest extant invertebrate relatives of the vertebrates. Their viruses may also reflect this transitional state. Yet, it is not known whether tunicate viruses are more closely related to vertebrate- or invertebrate-infecting viral lineages. We analysed primary and publicly available RNA libraries to extend the known diversity of tunicate-associated viruses and determine their relationship to viruses of other animals. We present evidence that influenza viruses, alphaviruses, and some mononegaviruses emerged prior to the evolution of vertebrates. We also show that the recombination of glycoproteins between different orders of RNA viruses, including between positive- and negative-sense viruses, may have shaped the evolution of multiple lineages. Our study reveals that some disease-causing RNA virus lineages were present in early chordates and highlights that the evolution of structural genes may be incongruent with that of the highly conserved RNA-dependent RNA polymerase.

microbiology↗

bioRxiv2024

Detection of exotic biosecurity threat ribgrass mosaic virus and novel tobamoviruses through metatranscriptomic sequencing of animal gut content

Ribgrass mosaic virus (RMV) and related viruses of the genus Tobamovirus (Virgaviridae) are cruciferous plant pathogens that represent a threat to global horticultural systems. In Australia, they are considered exotic biosecurity threats, and an incursion of these viruses would require rapid and strict control efforts. However, current surveillance methods for these viruses are limited. We examined whether RMV and related tobamoviruses could be detected by deep sequencing of gut metatranscriptomes of vertebrate animals and ticks. Using this method, we discovered that RMV, as well as a novel relative of RMV, and two highly diverse novel tobamoviruses are present in Australia. RMV was detected in multiple sites in both the Australian Capital Territory (ACT) and Tasmania, two regions separated by approximately 700km of land and 200km of water. The novel relative of RMV was detected in the ACT and New South Wales (NSW), while the highly divergent novel tobamoviruses were each detected in a single state, NSW and Queensland (QLD). In addition, Tobacco mild green mosaic virus, which is already known to be present in Australia, was detected in QLD using this method. This work highlights the potential utility of metatranscriptomic sequencing of wild animal gut for the surveillance of biosecurity threats to native and agricultural plant species. ImportancePlant viruses can have devastating impacts on global horticulture. Tobamoviruses (family Virgaviridae, genus Tobamovirus) are among the most damaging seed-borne viruses in horticultural crops, and Australia is free of many of the tobamoviruses that cause major crop losses in other countries. These viruses are extremely difficult to eradicate. Consequently, early detection of incursions is key to the control of these viruses in Australia, alongside rapid deployment of eradication and management plans. Current biosecurity surveillance methods in Australia rely on visual inspection, immunological assays, and molecular methods such as screening of imported seed lots. This study introduces a complementary approach that utilises unbiased metatranscriptomic sequencing of animal gut material to detect cryptic plant viruses circulating in nature. Using this approach, we detected five different tobamovirus circulating in Australia, including a virus thought to be exotic and three novel viruses. This unique approach highlights alternative options for surveillance/detection of exotic crop viruses.

microbiology↗

bioRxiv2024

Isolation of an infectious mammalian chu-like virus from tumor cells of the endangered Tasmanian devil (Sarcophilus harrisii)

Jingchuvirales (negative-sense RNA viruses) were initially discovered in invertebrates, with both exogenous and endogenous jingchuviruses subsequently identified in fish, reptiles and mammals. To date, jingchuviruses have only been described metagenomically. By screening primary tumor tissues and tumor cell lines from the endangered Tasmanian devil (Sarcophilus harrisii), we isolated Tasmanian devil chu-like virus (TDCV) from cultures of Tasmanian devil facial tumor disease (DFTD) cells. Cell infection experiments demonstrated active virus replication in Tasmanian devil tumor cells, but not mosquito cells. The absence of viral replication in fibroblasts in cell culture and the lack of RNA detection in several organs suggested that replication was associated with tumor cells. Phylogenetic analysis revealed that TDCV likely represents a novel virus family. This is the first isolation of a jingchuvirus, demonstrating their capacity to infect mammalian cells, and providing in vitro avenues to understand the biology of TDCV and its association with tumor cell infection.

microbiology↗

bioRxiv2024

Insect-specific Alphamesonivirus-1 (Mesoniviridae) in lymph node and lung tissues from two horses with acute respiratory syndrome

As members of the RNA virus order Nidovirales include those that infect hosts ranging from marine invertebrates to terrestrial mammals, understanding their emergence, host range and disease potential is of clear importance. The Mesoniviridae are a recently documented family of viruses within the Nidovirales. To date, mesoniviruses have only been associated with the infection of arthropods, particularly mosquitoes. Herein, we report the first detection of a mesonivirus - Alphamesonivirus-1 - in mammals. Specifically, we utilized genomic and histological techniques to identify the presence of Alphamesonivirus-1 in lung and lymph node tissues of two horses that succumbed to an acute respiratory syndrome. Notably, no other pathogens typically associated with respiratory disease in horses were detected in these samples. Counter to the previous contention that mesoniviruses only infect insects, our findings suggest a potentially broader host range and cross-species transmission of these viruses. The genome sequences of Alphamesonivirus-1 obtained from the two horses were closely related to those from a local Culex mosquito pool as well as an Alphamesonivirus-1 previously in identified Italy, suggestive of ongoing local transmission. The discovery of Alphamesonivirus-1 in tissues from diseased horses not only challenges current understandings of mesonivirus host range, but prompts further investigation into the role of insect-specific viruses in mammalian disease processes. Our results emphasize the importance of considering atypical pathogens in cases of unexplained animal deaths and suggest a potential zoonotic threat posed by previously overlooked viral families. IMPORTANCEAlphamesoniviruses, members of the Mesoniviridae family, have long been considered insect-specific viruses with no known association with vertebrate hosts. Herein, we describe the first detection of Alphamesonivirus-1 in mammals, marking a significant expansion of the known host range for this newly described virus family. Using detailed molecular and histological analyses we identified Alphamesonivirus-1 in lung and lymph node tissues of two horses that presented with an acute respiratory syndrome. Our findings indicate that Alphamesoniviruses may possess a broader host range than previously believed and could potentially induce severe disease in mammals. This unexpected host jump not only challenges existing knowledge on the ecology of mesoniviruses, but suggests that insect-specific viruses may pose a previously unrecognized health risk to vertebrates, including domesticated animals. These insights prompt the need for increased surveillance of atypical pathogens, especially in cases of unexplained respiratory illness, and may have implications for zoonotic disease emergence.

microbiology↗

bioRxiv2024

Genome sizes of animal RNA viruses reflect phylogenetic constraints

Animal genomes are characterized by extensive variation in size. RNA viruses similarly exhibit substantial genomic diversity, with genome lengths ranging from 1.7 to 64 Kb. Despite the myriad of novel viruses discovered by metagenomics, we know little of the factors that shape the evolution of the genome size in RNA viruses. We analyzed the variation in genome sizes across orders and families of animal RNA viruses. We found that RNA viruses can have highly variable genome sizes within and among orders, with the Nidovirales (including the Coronaviridae) having both significantly larger genomes and a greater range of genome sizes than other orders. In the Bunyavirales, Amarillovirales, Nidovirales and Picornavirales the genome sizes of invertebrate-associated RNA viruses were significantly larger than those that infect vertebrates, in contrast to their animal hosts in which vertebrates commonly have larger genomes than invertebrates. However, in the Mononegavirales, vertebrate viruses were significantly larger than those viruses associated with invertebrates. There were similarly complex associations between genome size and patterns of genome segmentation. In the Bunyavirales, Reovirales, and Nidovirales, viruses with segmented genomes or that possessed a large number of segments, had significantly larger genome sizes that viruses with non-segmented genomes or a small number of segments, while in the Articulavirales there were no significant differences in genome size among viruses possessing any number of genome segments. More broadly, our analysis revealed that taxonomic position (i.e., RNA virus order) had a greater impact on genome size than whether viruses infected vertebrates or invertebrates or their pattern of genome segmentation. Hence, the phylogenetic constraints on genome size are of sufficient magnitude to shape other aspects of virus evolution.

microbiology↗

bioRxiv2024

A virus associated with the zoonotic pathogen Plasmodium knowlesi causing human malaria is a member of a diverse and unclassified viral taxon

Apicomplexa are single-celled eukaryotes that can infect humans and include the mosquito-borne parasite Plasmodium, the cause of malaria. Increasing rates of drug resistance in human-only Plasmodium species are reducing the efficacy of control efforts and antimalarial treatments. There are also rising cases of P. knowlesi, the only zoonotic Plasmodium species that causes severe disease and death in humans. Thus, there is a need to develop additional innovative strategies to combat malaria. Viruses that infect non-Plasmodium spp. disease-causing protozoa have been shown to affect pathogen life cycle and disease outcomes. However, only one virus (Matryoshka RNA virus 1) has been identified in Plasmodium, and none have been identified in zoonotic Plasmodium species. The rapid expansion of the known RNA virosphere using structure- and artificial intelligence-based methods suggests that this dearth is due to the divergent nature of RNA viruses that infect protozoa. We leveraged these newly uncovered data sets to explore the virome of human-infecting Plasmodium species collected in Sabah, east (Borneo) Malaysia. We identified a highly divergent RNA virus in two human-infecting P. knowlesi isolates that is related to the unclassified group ormycoviruses. By characterising fifteen additional ormycoviruses identified in the transcriptomes of arthropods we show that this group of viruses exhibits a complex ecology at the arthropod-mammal interface. Through the application of artificial intelligence methods, we then demonstrate that the ormycoviruses are part of a diverse and unclassified viral taxon. This is the first observation of an RNA virus in a zoonotic Plasmodium species. By linking small-scale experimental data to large-scale virus discovery advances, we characterise the diversity and genomic architecture of an unclassified viral taxon. This approach should be used to further explore the virome of disease-causing Apicomplexa and better understand how protozoa-infecting viruses may affect parasite fitness, pathobiology, and treatment outcomes.

evolutionary biology↗

bioRxiv2024

Small mammals in biodiversity hotspot harbor viruses of epidemic potential

Metagenomic sequencing has transformed our understanding of viral diversity in wildlife and its threat to human health. Despite this progress, many studies have lacked systematic and ecologically informed sampling, which has left numerous potentially emergent viruses undiscovered, and the drivers of their ecology and evolution poorly understood. We conducted an extensive analysis of viruses in the lung, spleen, and gut of 1,688 animals from 38 mammalian species across 428 sites in Yunnan, China--a hotspot for zoonotic diseases. We identified 162 mammalian viral species, including 102 novel species and 24 posing potential risks to humans due to their relationships with known pathogens associated with serious diseases and their ability to cross major host species barriers. Our findings offer an in-depth view of virus organotropism, cross-species transmission, host sharing patterns, and the ecological factors influencing viral evolution, all of which are critical for anticipating and mitigating future zoonotic outbreaks.

microbiology↗

bioRxiv2024

SegFinder: an automated tool for identifying RNA virus genome segments through co-occurrence in multiple sequenced samples

Metagenomic sequencing has expanded the RNA virosphere, but many identified viral genomes remain incomplete, especially for segmented viruses. Traditional methods relying on sequence homology struggle to identify highly divergent segments and group them confidently within a single virus species. To address this, we developed a new bioinformatic tool - SegFinder - that identifies virus genome segments based on their common co-occurrence at similar abundance within segmented viruses. SegFinder successfully re-discovered all segments from a test data set of individual mosquito transcriptomes, which was also used to establish parameter thresholds for reliable segment identification. Using these optimal parameters, we applied SegFinder to 858 libraries from eight metagenomic sequencing projects, including vertebrates, invertebrates, plants, and environmental samples. Furthermore, we identified 108 (excluding RdRP) unique viral genome segments, of which 55 were novel and 32 showed no recognizable sequence homology to known sequences but which were verified by the presence of conserved sequences at the genome termini. SegFinder is also able to identify segmented genome structures in viruses previously considered to be predominantly unsegmented, and in doing so expanded the number of known families and orders of segmented RNA viruses, making it a valuable tool in an era of large-scale parallel sequencing.

bioinformatics↗

bioRxiv2024

VirID: Beyond Virus Discovery - An Integrated Platform for Comprehensive RNA Virus Characterization

RNA viruses exhibit vast phylogenetic diversity and can significantly impact public health and agriculture. However, current bioinformatics tools for viral discovery from metagenomic data frequently generate false positive virus results, overestimate viral diversity, and misclassify virus sequences. Additionally, current tools often fail to determine virus-host associations, which hampers investigation of the potential threat posed by a newly detected virus. To address these issues we developed VirID, a software tool specifically designed for the discovery and characterization of RNA viruses from metagenomic data. The basis of VirID is a comprehensive RNA-dependent RNA polymerase (RdRP) database to enhance a workflow that includes RNA virus discovery, phylogenetic analysis, and phylogeny-based virus characterization. Benchmark tests on a simulated data set demonstrated that VirID had high accuracy in profiling viruses and estimating viral richness. In evaluations with real-world samples, VirID was able to identity RNA viruses of all type, but also provided accurate estimations of viral genetic diversity and virus classification, as well as comprehensive insights into virus associations with humans, animals, and plants. VirID therefore offers a robust tool for virus discovery and serves as a valuable resource in basic virological studies, pathogen surveillance, and early warning systems for infectious disease outbreaks.

bioinformatics↗

bioRxiv2024

LucaOne: Generalized Biological Foundation Model with Unified Nucleic Acid and Protein Language

AbstractThe language of biology, encoded in DNA, RNA, and proteins, forms the foundation of life but remains challenging to decode due to its complexity. Traditional computational methods often struggle to integrate information across these molecules, limiting a comprehensive understanding of biological systems. Advances in Natural Language Processing (NLP) with pre-trained models offer new possibilities for interpreting biological language. Here, we introduce LucaOne, a pre-trained foundation model trained on nucleic acid and protein sequences from 169,861 species. Through large-scale data integration and semisupervised learning, LucaOne demonstrates an understanding of key biological principles, such as DNA-Protein translation. Using few-shot learning, it effectively comprehends the central dogma of molecular biology and performs competitively on tasks involving DNA, RNA, or protein inputs. Our results highlight the potential of unified foundation models to address complex biological questions, providing an adaptable framework for bioinformatics research and enhancing the interpretation of lifes complexity.

bioinformatics↗

bioRxiv2024

Viromes of Antarctic fish resembles the diversity found at lower latitudes

Antarctica harbours some of the most isolated and extreme environments on Earth, concealing a largely unexplored and unique component of the global animal virosphere. To understand the diversity and evolutionary histories of viruses in these polar species we determined the viromes of 11 Antarctic fish species with 248 samples collected from the Ross Sea region spanning the Perciformes, Gadiformes, and Scorpaeniformes orders. The continents shift southward and cooling temperatures over 20 million years ago led to a reduction in biodiversity and subsequent radiation of some marine fauna, such as the notothenioid fishes. Despite decreased host species richness in polar regions, we revealed a surprisingly complex virome diversity in Ross Sea fish, with the types and numbers of viruses per host species and individuals sampled comparable to that of fish in warmer marine environments with higher host community diversity. We also observed a higher number of closely related viruses likely representing instances of recent and historic host-switching events among Perciformes (all notothenioids) than in the Gadiformes, suggesting that rapid speciation events within this order generated closely related host species with few genetic barriers to cross-species transmission. Additionally, we identified novel genomic variation in an arenavirus with a split nucleoprotein sequence containing a stable helical structure, indicating potential adaptation of viral proteins to extreme temperatures. These findings enhance our understanding of virus evolution and virus-host interactions in response to environmental shifts, especially in less diverse ecosystems more vulnerable to the impacts of anthropogenic and climate changes.

microbiology↗

bioRxiv2024

Meta-transcriptomic analysis of companion animal infectomes reveals their diversity and potential roles in animal and human disease

Companion animals such as cats and dogs harbor diverse microbial communities that can potentially impact human health due to close and frequent contact. To better characterize their total infectomes and assess zoonotic risks, we performed meta-transcriptomic profiling on 239 samples from cats and dogs collected across China, comparing the similarities and differences between animal species (cats or dogs), sampling sites (rectal or oropharyngeal), and health status (healthy or diseased). We identified 24 viral species, 270 bacterial genera, and two fungal genera, including many known pathogens such as canine parvovirus, Clostridium difficile, and Candida albicans, as well as opportunistic pathogens such as canine vesivirus. Microbial compositions differed mainly according to sampling site (i.e., rectal and oropharyngeal swabs), and less so between host species and health status. Notably, we detected 27 potential zoonotic pathogens, such as alphacoronavirus 1, among all sampling sites, hosts, and health status, underscoring substantial zoonotic risks requiring surveillance. Overall, our meta-transcriptomic analysis reveals a landscape of actively transcribing microorganisms in major companion animals, including key pathogens, those with the potential for cross-species transmission, and possible zoonotic threats.

microbiology↗

bioRxiv2024

Limited transmission of microbial species among coral reef fishes from the Great Barrier Reef, Australia

Reef fishes account for one-third of all extant marine fishes and exhibit enormous biodiversity within a highly interactive ecosystem. Yet relatively little is known about the diversity and evolution of microbial species (bacteria, viruses, and eukaryotes) associated with reef fish, even though this may provide valuable insights into the factors that shape microbial communities within vertebrate hosts as well as the extent and pattern of cross-species transmission. Through metatranscriptomic sequencing we characterised the viruses, bacteria, and single-celled eukaryotes from 128 reef fish species inhabiting Lizard Island and Orpheus Island on the Great Barrier Reef, Australia. We assessed whether microbial communities differed between islands that are separated by approximately 450 kilometres, and to what extent viruses were able to emerge in new hosts. Notably, despite strong ecological interactions in the reef environment, and the presence of the same families and subfamilies of viruses and bacteria on both islands, there was minimal evidence for the cross-species transmission of individual microorganisms among fish species. An exception was the high prevalence of the bacterial pathogen Photobacterium damselae among apparently healthy cardinalfishes from both islands, indicating that these fish species are natural reservoirs within the reef system. Overall, these data suggest that reef fishes have microbial-host associations that arose prior to the formation of the Great Barrier Reef, leading to strong host barriers to cross-species microbial transmission even within a highly interactive and species-rich environment.

microbiology↗

bioRxiv2024

Mapping glycoprotein structure reveals defining events in the evolution of the Flaviviridae

Viral glycoproteins drive membrane fusion in enveloped viruses and determine host range, tissue tropism and pathogenesis. Despite their importance, there is a fragmentary understanding of glycoproteins within the Flaviviridae; for many species the glycoproteins have not yet been identified, for others, such as the hepaciviruses, the molecular mechanisms of membrane fusion remain uncharacterised. Here, we combine comprehensive phylogenetic analyses with systematic protein structure prediction to survey glycoproteins across the entire Flaviviridae. We discover class-II fusion systems, homologous to the orthoflavivirus E glycoprotein, in most species, including highly-divergent jingmenviruses and large genome flaviviruses. However, the E1E2 glycoproteins of the hepaci-, pegi- and pestiviruses are structurally distinct, may represent a novel class of fusion mechanism, and are strictly associated with infection of vertebrate hosts. By mapping glycoprotein distribution onto the underlying phylogeny we reveal a complex history of evolutionary events that have shaped the diverse virology and ecology of the Flaviviridae.

microbiology↗