Biology subjects

Rose, K.

Publications and source records attributed to Rose, K..

At least 19 recordsLinked to original sources

bioRxiv2026

Epigenetic regulation of DPP4 receptor expression by NONO enables replication of MERS-CoV

Middle East respiratory syndrome coronavirus (MERS-CoV), first reported in 2012, belongs to the Betacoronavirus genus, including SARS-CoV and SARS-CoV-2. Human-to-human transmission of MERS-CoV appears inefficient, but repeated spillover events have been reported from at least 27 countries, raising concern for future emergent events. Coronaviruses (CoVs) rely extensively on host proteins to support their replication. Several studies have implicated the paraspeckle non-POU domain-containing octamer-binding protein (NONO) as an RNA-binding protein (RBP) that binds to CoV genomes, but the role of this protein in regulating replication is unknown. Here, we show that NONO is required for expression of dipeptidyl peptidase 4 (DPP4, also known as CD26), the major cellular receptor required for MERS-CoV attachment and entry. NONO did not impact DPP4 mRNA processing or stability but instead promoted DPP4 transcription through control of active H3K4me3 and repressive H3K27me3 histone modifications at the DPP4 locus. Together, these findings identify NONO as a key proviral host factor for MERS-CoV and reveal an epigenetic mechanism linking a host RBP to viral entry receptor expression that may represent a target for therapeutic strategies.

microbiology↗

bioRxiv2026

Microbiome histidine competition mediates dietary control of systemic imidazole propionate

The gut microbiome produces numerous metabolites that influence mammalian health. While microbiome composition and diet influence metabolite concentrations, how these factors interact remains incompletely defined. Here we find production of imidazole propionate (ImP), a microbial metabolite associated with cardiometabolic and neurodegenerative diseases, is determined by the balance of competing metabolic pathways that catabolize histidine to ImP or short-chain fatty acids (SCFAs). We show glutamate serves as a preferred substrate that selectively inhibits histidine conversion to SCFAs, redirecting flux to increased ImP production across mouse- and human-derived microbial communities. We find dietary monosodium glutamate (MSG) acting via this mechanism boosts ImP production in the mouse gut, transiently impairing glucose tolerance and increasing systemic ImP. These findings show that predictable interactions between dietary substrate and microbial competition control systemic ImP levels, providing a mechanistic framework for understanding microbiome metabolite production more broadly.

microbiology↗

bioRxiv2026

Hidden diversity and expanded host range of sarthroviruses, including terrestrial vertebrates

The Sarthroviridae are a family of highly compact satellite RNA viruses comprising one recognised species, extra small virus (XSV). Macrobrachium rosenbergii nodavirus (MrNV) is the associated helper virus of XSV and their co-infection has been linked to white tail disease in freshwater prawns globally, although the role of XSV is remains unclear. Here, we describe the discovery and characterisation of ten novel, highly divergent sarthrovirus species from a range of hosts and environments within a small geographical region in Australia. These comprise novel sarthroviruses associated with marine sponges, seal and dingo faeces, environmental marine sediment samples and Indo-Pacific geckos (Hemidactylus garnotii). All the novel viruses possess only a capsid protein, consistent with the genome of XSV, yet exhibit substantial sequence divergence. Notably, some sarthrovirus variants seem to utilise different replication systems despite being genetically identical and present in the same host species. Sequences from nodaviruses, which could plausibly act as helpers, were associated with some, but not all, the sarthroviruses identified here. Phylogenetic analyses support the expansion of the Sarthroviridae into multiple distinct lineages, comprising at least seven genera. Collectively, these findings reveal a broader ecological distribution and evolutionary diversity of sarthroviruses and highlight the possibility of alternative replication strategies and tissue tropism in diverse animal host. SignificanceSarthoviruses are small ([~]800 nucleotides) satellite RNA viruses associated with a nodavirus of crustaceans that acts as a helper. To date, the only known sarthovirus is extra small virus (XSV), which also represents the sole species within the Sarthroviridae. Here, we report the detection of ten divergent sarthroviruses sampled from diverse animal hosts, including vertebrates, that expand the family to 11 species and at least seven genera. These viruses were detected from various host taxa and environmental samples from a confined geographical region in eastern Australia, suggesting that they are ecologically connected. Notably, we did not detect nodaviruses in all samples containing sarthroviruses, suggesting that different viruses may act as helpers for sarthovirus replication.

microbiology↗

bioRxiv2026

Detection and genomic characterisation of a novel hantavirus in Australian dolphins

We report the detection of a novel hantavirus in the lung tissue of two diseased Australian dolphins with histopathological changes. Phylogenetic analysis placed this virus within the genus Mobatvirus. This highlights the ability of hantaviruses to infect non-terrestrial mammals and the potential role of marine mammals as one health sentinels.

microbiology↗

bioRxiv2026

Co-Circulation of Multiple Kolmioviridae Lineages Through Vertebrate Evolution

Although once only characterized by human hepatitis deltavirus (HDV), membership of the family Kolmioviridae has dramatically expanded in recent years. Despite this transformation in our understanding of the host range of kolmioviruses, the evolutionary history of this enigmatic group of RNA viruses is unclear. Kolmioviruses are characterized as small ([~]1.7kb) satellite viruses that encode a single [~]200 amino acid delta antigen (DAg) and require unrelated helper viruses for replication. Here, we describe eight novel kolmioviruses from metatranscriptomic studies of the American alligator (Alligator missippiensis), red kangaroo (Osphranter rufus), and central bearded dragon (Pogona vitticeps), as well as avian kolmioviruses mined from the Sequence Read Archive (SRA). Although the novel kolmioviruses were often found in samples co-infected by other viruses, there was no evidence for the presence of hepatitis B virus as seen in HDV. By employing a range of sequence data sets, alignment methods, alignment trimming methods, and substitution models, we provide an evolutionary history of the Kolmioviridae that maximizes the extent of virus-host co-divergence and refines estimates of their evolutionary timescale. Although DAg amino acid sequences are more conserved than nucleotide sequences and hence might be expected to result in more accurate phylogenetic trees, we show that full genome nucleotide sequences likely provide the best representation of kolmiovirus evolution. More broadly, our results reveal that irrespective of the data set used, multiple distinct kolmiovirus lineages have co-circulated throughout vertebrate evolution over timescales spanning hundreds of millions of years, with the association between HDV and HBV appearing only recently. Significance StatementKolmioviruses are satellite RNA viruses, with hepatitis deltavirus (HDV) associated with human disease following co-infection with hepatitis B virus (HBV) the best characterized. Although a growing number of animal kolmioviruses have been identified in metagenomic studies and associated with a range of helper viruses, the evolutionary origins and history of this important and unique group of viruses is unknown. By identifying novel kolmioviruses in a range vertebrate hosts, including American alligators, we show that highly diverse lineages of kolmioviruses have co-circulated for the duration of vertebrate evolution with clear evidence of virus-host co-divergence, and are associated with a variety of potential helper viruses. Despite this antiquity, we present evidence that the HDV-HBV association only recently evolved in human populations.

microbiology↗

bioRxiv2025

In situ cryo-ET visualization of mitochondrial depolarization and mitophagic engulfment

Defective mitochondrial quality control in response to loss of mitochondrial membrane polarization is implicated in Parkinsons disease by mutations in PINK1 and PRKN. Application of in situ cryo-electron tomography (cryo-ET) made it possible to visualize the consequences of mitochondrial depolarization at higher resolution than heretofore attainable. Parkin-expressing U2OS cells were treated with the depolarizing agents oligomycin and antimycin A (OA), subjected to cryo-FIB milling, and mitochondrial structure was characterized by in situ cryo-ET. Phagophores were visualized in association with mitochondrial fragments. Bridge-like lipid transporter (BLTP) densities potentially corresponding to ATG2A were seen connected to mitophagic phagophores. Mitochondria in OA-treated cells were fragmented and devoid of matrix calcium phosphate crystals. The intermembrane gap of cristae was narrowed and the intermembrane volume reduced, and some fragments were devoid of cristae. A subpopulation of ATP synthases re-localized from cristae to the inner boundary membrane (IBM) apposed to the outer membrane (OMM). The structure of the dome-shaped prohibitin complex, a dodecamer of PHB1-PHB2 dimers, was determined in situ by sub-tomogram averaging in untreated and treated cells and found to exist in open and closed conformations, with the closed conformation is enriched by OA treatment. These findings provide a set of native snapshots of the manifold nano-structural consequences of mitochondrial depolarization and provide a baseline for future in situ dissection of Parkin-dependent mitophagy.

cell biology↗

bioRxiv2025

Limited diversity of bat-associated RNA viruses in endangered and geographically isolated Christmas Island flying foxes

Bats are commonly thought to harbour a high diversity and abundance of RNA viruses, some of which are able to jump species boundaries to emerge in new hosts. However, gaps remain in our understanding of the ecological factors that shape the bat virome and influence the diversity, circulation and persistence of viral infections. Flying foxes (Pteropodidae) are representative of the chiropteran fauna in Australia, holding significant ecological, cultural, and social importance. However, some species have also been linked to the circulation of mammalian pathogens such as Hendra virus and Australian bat lyssavirus. Here, we characterised the virome of the Christmas Island flying fox (Pteropus melanotus natalis), an endemic and endangered species only found on the remote Australian territory of Christmas Island. Through metatranscriptomic sequencing of 46 samples, including faeces, blood, urine and tissue lesions, we found that these bats exhibit limited RNA virus diversity dominated by dietary viruses. The paucity of RNA viruses likely results from their small population size (between 1500 and 2600 individuals) and the virtual geographic isolation from other bat and mammalian species, except for pests and humans. However, we identified a novel alphacoronavirus in urine, related to viruses circulating in microbats in mainland Australia, and a picorna-like virus related to picornaviruses found in invertebrates. Although this novel picorna-like virus may be of a dietary origin, these flying foxes predominantly eat nectar, pollen and fruit, and viral RNA was also present in blood, urine and wing lesion samples, such that a broader tropism cannot be excluded. Overall, these data reveal how ecological factors have a profound impact on RNA virome diversity, highlighting risks to bat conservation, and showing that bats are not always persistent reservoirs for zoonotic viruses.

microbiology↗

bioRxiv2023

Identification of a novel papillomavirus from a New Zealand fur seal (Arctocephalus forsteri) with oral papilloma-like lesions

Despite being the predominant seal species in the Australian-New Zealand region and serving as a key indicator of marine environmental health, little is known about infectious diseases in New Zealand fur seals (Long-nosed fur seal; Arctocephalus forsteri). Several papillomaviruses have been identified in earless seals and sea lions, with the latter linked to cutaneous plaques and invasive squamous cell carcinoma. To date, no papillomaviruses have been reported in fur seals. We used traditional veterinary diagnostic techniques and metatranscriptomic sequencing of tissue samples to investigate the virome of New Zealand fur seals. We identified a novel papillomavirus, provisionally termed Arctocephalus forsteri papillomavirus 1 (AfPV1) in an animal with clinically and histologically identified oral papilloma-like lesions. RT-PCR confirmed the presence of AfPV1 only in oral papilloma samples from the affected individual. Phylogenetic analysis of the complete 7,926 bp genome of AfPV1 revealed that it clustered with taupapillomaviruses found in related Carnivora species. In addition, we identified the partial genome of a novel Gammaherpesvirus, Arctocephalus forsteri gammaherpesvirus 1 (AfGHV1), in a different individual without pathological evidence of viral infection. These findings highlight the need for further research into the disease associations and impact of undiagnosed and novel viruses on New Zealand fur seals.

microbiology↗

bioRxiv2023

A RAB7A Phosphoswitch Coordinates Rubicon Homology Protein Regulation of PINK1/Parkin-Dependent Mitophagy

Activation of PINK1 and Parkin in response to mitochondrial damage initiates a cytoprotective mitophagy response that includes phosphorylation of RAB7A at Ser72. Rubicon is a RAB7A binding protein that acts as a negative regulator of autophagy. The structure of the Rubicon-RAB7A complex suggests that phosphorylation of RAB7A at Ser72 would block Rubicon binding. Indeed, in vitro phosphorylation of RAB7A by TBK1 abrogates Rubicon-RAB7A binding. Pacer, a positive regulator of autophagy, has an RH domain with a basic triad predicted to bind an introduced phosphate. Consistent with this, Pacer-RH binds to phosho-RAB7A but not to unphosphorylated RAB7A. In cells, mitochondrial depolarization reduces Rubicon:RAB7A colocalization whilst recruiting Pacer to phospho-RAB7A-positive puncta. Pacer knockout reduces Parkin mitophagy with little effect on bulk autophagy or Parkin-independent mitophagy. Rescue of Parkin-dependent mitophagy requires the intact pRAB7A phosphate-binding basic triad of Pacer. Together these structural and functional data support a model in which the TBK1-dependent phosphorylation of RAB7A serves as a switch, promoting mitophagy by relieving Rubicon inhibition and favoring Pacer activation.

cell biology↗

bioRxiv2023

Tau fibrils induce nanoscale membrane damage and nucleate cytosolic tau at lysosomes

The prion-like spread of protein aggregates is a leading hypothesis for the propagation of neurofibrillary lesions in the brain, including the spread of tau inclusions associated with Alzheimers disease. The mechanisms of cellular uptake of tau seeds and subsequent nucleated polymerization of cytosolic tau are major questions in the field, and the potential for coupling between the entry and nucleation mechanisms has been little explored. We found that in primary astrocytes, endocytosis of tau seeds leads to their accumulation in lysosomes. This in turn leads to lysosomal swelling, deacidification and recruitment of ESCRT proteins, but not Galectin-3, to the lysosomal membrane. These observations are consistent with nanoscale damage of the lysosomal membrane. Using live cell and STORM, imaging, nucleation of cytosolic tau occurs primarily at the lysosome membrane under these conditions. These data suggest that tau seeds escape from lysosomes via nanoscale damage rather than wholesale rupture, and that nucleation of cytosolic tau commences as soon as tau fibril ends emerge from the lysosomal membrane.

cell biology↗

bioRxiv2022

Transcriptional activity mediated by beta-CATENIN and TCF/LEF family members is completely dispensable for survival of multiple human colorectal cancer cell lines

Unrestrained transcriptional activity of {beta}-CATENIN and its binding partner TCF7L2 frequently underlies colorectal tumor initiation and is considered an obligatory oncogenic driver throughout intestinal carcinogenesis. Yet, the TCF7L2 gene carries inactivating mutations in about 10 % of colorectal tumors and is non-essential in colorectal cancer (CRC) cell lines. To determine whether CRC cells acquire TCF7L2-independence through cancer-specific compensation by other T-cell factor (TCF)/lymphoid enhancer-binding factor (LEF) family members, or rather lose addiction to {beta}-CATENIN/TCF7L2-driven gene expression altogether, we generated multiple CRC cell lines entirely negative for TCF/LEF or {beta}-CATENIN expression. Viability of these cells demonstrates complete {beta}-CATENIN- and TCF/LEF-independence, albeit one {beta}-CATENIN-deficient cell line eventually became senescent. Absence of TCF/LEF proteins and {beta}-CATENIN consistently impaired CRC cell proliferation, reminiscent of mitogenic effects of WNT/{beta}-CATENIN signaling in the healthy intestine. Despite this common phenotype, {beta}-CATENIN-deficient cells exhibited highly cell-line-specific gene expression changes with little overlap between {beta}-CATENIN- and TCF7L2-dependent transcriptomes. Apparently, {beta}-CATENIN and TCF7L2 control sizeable fractions of their target genes independently from each other. The observed divergence of {beta}-CATENIN and TCF7L2 transcriptional programs, and the finding that neither {beta}-CATENIN nor TCF/LEF activity is strictly required for CRC cell survival has important implications when evaluating these factors as potential drug targets.

cell biology↗

bioRxiv2022

Gammaretroviruses, novel viruses and pathogenic bacteria in Australian bats with neurological signs, pneumonia and skin lesions

More than 70 bat species are found in mainland Australia, including five species of megabat from a single genus (family Pteropodidae) and more than 65 species representing six families of microbats. The conservation status of these animals varies from least concern to endangered. Research directed at evaluating the impact of microorganisms on bat health has been generally restricted to surveillance for specific pathogens. While most of the current bat virome studies focus on sampling apparently healthy individuals, little is known about the infectome of diseased bats. We performed traditional diagnostic techniques and metatranscriptomic sequencing on tissue samples from 43 individual bats, comprising three flying fox and two microbat species experiencing a range of disease syndromes, including mass mortality, neurological signs, pneumonia and skin lesions. We identified reads from four pathogenic bacteria and two pathogenic fungi, including Pseudomonas aeruginosa in lung samples from flying foxes with peracute pneumonia, and with dermatitis. Of note, we identified the recently discovered Hervey pteropid gammaretrovirus, with evidence of replication consistent with an exogenous virus, in a bat with lymphoid leukemia. In addition, one novel picornavirus, at least three novel astroviruses and bat pegiviruses were identified. We suggest that the most likely cause of peracute lung disease was Pseudomonas aeruginosa, while we suspect Hervey pteropid gammaretrovirus was associated with lymphoid leukemia. It is possible that any of the novel astroviruses could have contributed to the presentation of skin lesions in individual microbats. This study highlights the importance of studying the role of microorganisms in bat health and conservation. IMPORTANCEBats have been implicated as reservoir hosts for zoonotic disease of concern, however, the burden of microorganism including viruses on bat health and disease is understudied. Here we incorporated veterinary diagnostics and RNA sequencing to identify the presence of microbes and viruses with possible pathogenic status in Australian bats with varying disease presentations. These techniques were able to effectively identify and describe several pathogenic species of bacteria and fungi in addition to known and novel viruses. This study emphasises the importance of screening pathogens in cases of bat mortality for the conservation of this diverse order.

microbiology↗

bioRxiv2022

In vitro reconstitution of calcium-dependent recruitment of the human ESCRT machinery in lysosomal membrane repair

The endosomal sorting complex required for transport (ESCRT) machinery has been shown to be centrally involved in repair of damage to both the plasma and lysosome membranes. ESCRT recruitment to sites of damage occurs on a fast time scale, and Ca2+ has been proposed to play a key signaling role in the process. Here, we show that the Ca2+-binding regulatory protein ALG-2 binds directly to negatively charged membranes in a Ca2+-dependent manner. Next, by monitoring the colocalization of ALIX with ALG-2 on negatively charged membranes, we show that ALG-2 recruits ALIX to the membrane. Furthermore, we show that ALIX recruitment to membrane orchestrates the downstream assembly of late-acting CHMP4B, CHMP3, CHMP2A subunits along with the AAA+ ATPase VPS4B. Finally, we show that ALG-2 can also recruit the ESCRT-III machinery to the membrane via the canonical ESCRT-I/II pathway. Our reconstitution experiments delineate the minimal sets of components needed to assemble the entire membrane repair machinery and open a new avenue for mechanistic understanding of endolysosomal membrane repair. Significance statementOne of the ways by which protein aggregates can propagate and lead to progression of a neurodegenerative disease is by damaging the membrane that is destined to degrade the misfolded, aggregated protein. ESCRT machinery has been implicated in sealing these damaged membranes, and the nature of the membrane recruitment trigger signal for this machinery is a major open question. Here, we show in vitro that ALG-2 can bring ESCRT machinery to membranes in a Ca2+-dependent manner.

cell biology↗

bioRxiv2021

Animal lifestyle changes acceptable mass limits for attached tags

O_LIAnimal-attached devices have transformed our understanding of vertebrate ecology. To minimize tag-related harm for these studies, researchers have long advocated that tag masses should not exceed 3% of the animals body mass. However, this proposition ignores tag forces generated as a result of animal movement. C_LIO_LIUsing data from collar-attached accelerometers on diverse free-ranging terrestrial animals, we detail a tag-based acceleration method (TbAM) in which we quantify animal athleticism in terms of fractions of animal movement time devoted to different collar-recorded accelerations. The varying accelerations are converted to forces imposed on the animals based on the acceleration and tag mass and allow derivation of defined force limits, including those amounting to 3% of the animals mass, for specified fractions of any animals active time. C_LIO_LIWe demonstrate how species athleticism is the principal determinant of tag forces, whereas body mass is of little importance. Forces exerted by 3% tags were mostly equivalent to 4-19% of the animals masses during moving, with a maximum of 54% in a hunting cheetah. Cumulative frequency curves of tag acceleration for periods when animals were active, all showed a characteristic sigmoid pattern, which was displaced further to the right as higher acceleration activities accounted for an increasing proportion of any animals time. Specifying that tags should exert forces that are less than 3% of the animals body mass for 95% of the time led to corrected tag masses constituting between 1.6% and 2.98% of our study animals masses, with values depending on animal athleticism. C_LIO_LIRecognition that animal athleticism affects tag forces of their carriers fundamentally changes how acceptable tag mass limits should be determined by ethics bodies. In order to have a scientifically robust acceptable threshold to limit the forces experienced by an animal carrier, we suggest practitioners derive a similar cumulative acceleration profile for their study species and use a minimum of the 95% limits on the plot (although higher limits may be more appropriate). C_LI

zoology↗

bioRxiv2020

gEAR: gene Expression Analysis Resource portal for community-driven, multi-omic data exploration

The gEAR portal (gene Expression Analysis Resource, umgear.org) is an open access community-driven tool for multi-omic and multi-species data visualization, analysis and sharing. The gEAR supports visualization of multiple RNA-seq data types (bulk, sorted, single cell/nucleus) and epigenomics data, from multiple species, time points and tissues in a single-page, user-friendly browsable format. An integrated scRNA-seq workbench provides access to raw data of scRNA-seq datasets for de novo analysis, as well as marker-gene and cluster comparisons of pre-assigned clusters. Users can upload, view, analyze and privately share their own data in the context of previously published datasets. Short, permanent URLs can be generated for dissemination of individual or collections of datasets in published manuscripts. While the gEAR is currently curated for auditory research with over 90 high-value datasets organized in thematic profiles, the gEAR also supports the BRAIN initiative (via nemoanalytics.org) and is easily adaptable for other research domains.

bioinformatics↗

bioRxiv2020

Meta-transcriptomic discovery of a divergent circovirus and a chaphamaparvovirus in captive reptiles with proliferative respiratory syndrome

Viral pathogens are being increasingly described in association with mass morbidity and mortality events in reptiles. However, our knowledge of reptile viruses and their role in population health remains limited. Herein, we describe a meta-transcriptomic investigation of a mass morbidity and mortality event in a colony of central bearded dragons (Pogona vitticeps) in 2014. Severe, extensive proliferation of the respiratory epithelium was consistently found in affected dragons. Similar proliferative lung lesions were identified in bearded dragons from the same colony in 2020 in association with increased intermittent mortality. Total RNA sequencing of bearded dragon tissue identified two divergent DNA viruses: a reptile-infecting circovirus, denoted bearded dragon circovirus (BDCV), and the first exogeneous reptilian chaphamaparvovirus - bearded dragon chaphamaparvovirus (BDchPV). Phylogenetic analysis revealed that BDCV was most closely related to bat-associated circoviruses, exhibiting 70% amino acid sequence identity. In contrast, the newly discovered BDchPV showed approximately 35-40% identity in the non-structural (NS) protein to parvoviruses obtained from tilapia fish and crocodiles in China. Subsequent specific PCR assays detected BDCV exclusively and comprehensively within animals with proliferative pulmonary lesions and respiratory disease. This study expands our understanding of viral diversity in the context of diseased reptiles in captivity.

microbiology↗

bioRxiv2020

Metagenomic identification of diverse animal hepaciviruses and pegiviruses

The RNA virus family Flaviviridae harbours several important pathogens of humans and other animals, including Zika virus, dengue virus and hepatitis C virus. The Flaviviridae are currently divided into four genera - Hepacivirus, Pegivirus, Pestivirus and Flavivirus - each of which have a diverse host range. Members of the genus Hepacivirus are associated with a diverse array of animal species, including humans and non-human primates, other mammalian species, as well as birds and fish, while the closely related pegiviruses have been identified in a variety of mammalian taxa including humans. Using a combination of meta-transcriptomic and whole genome sequencing we identified four novel hepaciviruses and one novel variant of a known virus, in five species of native Australian wildlife, expanding our knowledge of the diversity in this important group of RNA viruses. The infected hosts comprised native Australian marsupials and birds, as well as a native gecko (Gehyra lauta). The addition of these novel viruses led to the identification of a distinct marsupial clade within the hepacivirus phylogeny that also included an engorged Ixodes holocyclus tick collected while feeding on Australian long-nosed bandicoots (Perameles nasuta). Gecko and avian associated hepacivirus lineages were also identified. In addition, by mining the short-read archive (SRA) database we identified another five novel members of Flaviviridae, comprising three new hepaciviruses from avian and primate hosts, as well as two primate-associated pegiviruses. The large-scale phylogenetic analysis of these novel hepacivirus and pegivirus genomes provides additional support for virus-host co-divergence over evolutionary time-scales.

microbiology↗

bioRxiv2020

Meta-transcriptomic analysis of virus diversity in urban wild birds with paretic disease

Wild birds are major natural reservoirs and potential dispersers of a variety of infectious diseases. As such, it is important to determine the diversity of viruses they carry and use this information to help understand the potential risks of spill-over to humans, domestic animals, and other wildlife. We investigated the potential viral causes of paresis in long-standing, but undiagnosed disease syndromes in wild Australian birds. RNA from diseased birds was extracted and pooled based on tissue type, host species and clinical manifestation for metagenomic sequencing. Using a bulk and unbiased meta-transcriptomic approach, combined with careful clinical investigation and histopathology, we identified a number of novel viruses from the families Astroviridae, Picornaviridae, Polyomaviridae, Paramyxoviridae, Parvoviridae, Flaviviridae, and Circoviridae in common urban wild birds including Australian magpies, magpie lark, pied currawongs, Australian ravens, and rainbow lorikeets. In each case the presence of the virus was confirmed by RT-PCR. These data revealed a number of candidate viral pathogens that may contribute to coronary, skeletal muscle, vascular and neuropathology in birds of the Corvidae and Artamidae families, and neuropathology in members of the Psittaculidae. The existence of such a diverse virome in urban avian species highlights the importance and challenges in elucidating the etiology and ecology of wildlife pathogens in urban environments. This information will be increasingly important for managing disease risks and conducting surveillance for potential viral threats to wildlife, livestock and human health. More broadly, our work shows how meta-transcriptomics brings a new utility to pathogen discovery in wildlife diseases. ImportanceWildlife naturally harbor a diverse array of infectious microorganisms and can be a source of novel diseases in domestic animals and human populations. Using unbiased RNA sequencing we identified highly diverse viruses in native birds in Australian urban environments presenting with paresis. This investigation included the clinical investigation and description of poorly understood recurring syndromes of unknown etiology: clenched claw syndrome, and black and white bird disease. As well as identifying a range of potentially disease-causing viral pathogens, this study describes methods that can effectively and efficiently characterize emergent disease syndromes in free ranging wildlife, and promotes further surveillance for specific potential pathogens of potential conservation and zoonotic concern.

microbiology↗