ORCID Profile
0000-0003-3325-2311
Current Organisation
University of Nottingham
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Publisher: Springer Science and Business Media LLC
Date: 19-07-2016
Publisher: Springer Science and Business Media LLC
Date: 07-12-2016
DOI: 10.1038/ONC.2015.457
Abstract: The tumor suppressor p53 is mutated in ~50% of human cancers. P53 is activated by a range of stimuli and regulates several cellular processes, including apoptotic cell death, cell cycle arrest, senescence and DNA repair. P53 induces apoptosis via transcriptional induction of the BH3-only proteins PUMA (p53-upregulated modulator of apoptosis) and NOXA, and cell cycle arrest via p21. Induction of these processes was proposed to be critical for p53-mediated tumor suppression. It is therefore surprising that mice lacking PUMA, NOXA and p21, as well as mice bearing mutations in p53 that impair the transcriptional activation of these genes, are not tumor prone, unlike mice lacking p53 function, which spontaneously develop tumors with 100% incidence. These p53 target genes and the processes they regulate may, however, impact differently on tumor development depending on the oncogenic drivers. For ex le, loss of PUMA enhances c-MYC-driven lymphoma development in mice, but, interestingly, the acceleration was less impressive compared with that caused by the loss of even a single p53 allele. Different studies have reported that loss of p21 can accelerate, delay or have no impact on tumorigenesis. In an attempt to resolve this controversy, we examined whether loss of p21-mediated cell cycle arrest cooperates with PUMA deficiency in accelerating lymphoma development in Eμ-Myc mice (overexpressing c-MYC in B-lymphoid cells). We found that Eμ-Myc mice lacking both p21 and PUMA (Eμ-Myc Puma(-/-) 21(-/-)) developed lymphoma at a rate comparable to Eμ-Myc Puma(-/-) animals, notably with considerably longer latency than Eμ-Myc 53(+/-)mice. Loss of p21 had no impact on the numbers, cycling or survival of pre-leukemic Eμ-Myc B-lymphoid cells, even when PUMA was lost concomitantly. These results demonstrate that even in the context of deregulated c-MYC expression, p53 must suppress tumor development by activating processes apart from, or in addition to, PUMA-mediated apoptosis and p21-induced cell cycle arrest.
Publisher: Wiley
Date: 20-06-2022
DOI: 10.1002/VRO2.39
Abstract: Schmallenberg virus (SBV) is a midge‐borne arbovirus that first emerged in the European ruminant population in 2011 and has since settled to an endemic pattern of disease outbreaks on an approximately 4‐year cycle when herd immunity from the previous circulation drops to a point allowing renewed widescale virus circulation. The impacts of trade restrictions on genetic products (semen, embryos) from affected areas were severe, particularly after the discovery that the virus is intermittently shed in the semen of a small number of bulls. The trade in small ruminant (ram and goat) semen is less than that of bulls nonetheless, there has been no study into the shedding rate of SBV in ram semen. Semen s les ( n = 65) were collected as part of UK ram trials and artificial insemination studies around the period of the 2016–2018 SBV recirculation. Semen was preserved in RNA later for shipping, and RNA extraction with RNeasy and S gene RT‐quantitative PCR performed for SBV nucleic acid detection. No SBV RNA was detected in any s les. While larger numbers of animals would be needed to completely exclude the possibility of SBV shedding in ram semen, this trial nonetheless highlights that this is likely a rare event if it occurs at all and is unlikely to play a role in disease transmission.
Publisher: Wiley
Date: 21-02-2023
DOI: 10.1002/VETR.2731
Abstract: Small ruminant lentiviruses (SRLVs) are lentiviruses of sheep and goats, formerly known as maedi–visna (MV) in sheep and caprine encephalitis and arthritis in goats. In sheep, SRLVs commonly cause progressive pneumonia, wasting and indurative mastitis. SRLVs have a long latent period, and chronic production losses are often not recognised until very late. Few studies quantifying the production losses in ewes have been published, and none have been published under UK flock husbandry conditions. Production records of milk yield and somatic cell count (SCC) from a dairy flock of 319 milking East Friesian × Lacaune ewes identified as MV infected via routine serological screening for SRLV antibodies were used in multivariable linear regression modelling to estimate the impact of SRLV status on total milk yield and SCC. Milk yield was reduced in seropositive ewes by 8.1%–9.2% over an entire lactation. SCC counts were not significantly different in SRLV‐infected and unifected animals. Further parameters, such as body condition score or clinical mastitis, that were not available may have clarified the underlying cause of milk yield drop. The study demonstrates substantial production losses in an SRLV‐affected flock and highlights the impact of the virus on a farm's economic viability.
Publisher: Springer Science and Business Media LLC
Date: 26-02-2021
DOI: 10.1038/S41467-021-21612-7
Abstract: Repeated retroviral infections of vertebrate germlines have made endogenous retroviruses ubiquitous features of mammalian genomes. However, millions of years of evolution obscure many of the immediate repercussions of retroviral endogenisation on host health. Here we examine retroviral endogenisation during its earliest stages in the koala ( Phascolarctos cinereus ), a species undergoing germline invasion by koala retrovirus (KoRV) and affected by high cancer prevalence. We characterise KoRV integration sites (IS) in tumour and healthy tissues from 10 koalas, detecting 1002 unique IS, with hotspots of integration occurring in the vicinity of known cancer genes. We find that tumours accumulate novel IS, with proximate genes over-represented for cancer associations. We detect dysregulation of genes containing IS and identify a highly-expressed transduced oncogene. Our data provide insights into the tremendous mutational load suffered by the host during active retroviral germline invasion, a process repeatedly experienced and overcome during the evolution of vertebrate lineages.
Publisher: MDPI AG
Date: 23-07-2019
DOI: 10.3390/V11070675
Abstract: Nephropathia Epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS) and linked to hantavirus infection, is endemic in the Republic of Tatarstan. Several genetic markers of HFRS severity have been identified previously, including human leukocyte antigen (HLA) complexes and nucleotide polymorphism in the tumor necrosis factor alpha (TNFα) gene. Still, our understanding of the genetic markers of NE severity remains incomplete. The frequency of the C–C chemokine receptor type 5 (CCR5) gene wild type and gene with 32-base-pair deletion (Δ32CCR5) genotypes in 98 NE s les and 592 controls was analyzed using PCR. Along with the serum levels of 94 analytes, a lack of differences in the CCR5 genotype distribution between NE cases and the general population suggests that the CCR5 genotype does not affect susceptibility to hantavirus infection. However, in NE cases, significant variation in the serum levels of the host matrix metalloproteases between functional CCR5 homozygous and Δ32CCR5 heterozygous patients was detected. Also, the oliguric phase was longer, while thrombocyte counts were lower in functional CCR5 homozygous as compared to heterozygous NE cases. Our data, for the first time, presents the potential role of the CCR5 receptor genotype in NE pathogenesis. Our data suggests that NE pathogenesis in functional CCR5 homozygous and heterozygous NE patients differs, where homozygous cases may have more disintegration of the extracellular matrix and potentially more severe disease.
Publisher: Cold Spring Harbor Laboratory
Date: 09-11-2017
DOI: 10.1101/211466
Abstract: Koala retrovirus (KoRV) is unique amongst endogenous (inherited) retroviruses in that its incorporation to the host genome is still active, providing an opportunity to study what drives this fundamental process in vertebrate genome evolution. Animals in the southern part of the natural range of koalas were previously thought to be either virus free or to have only exogenous variants of KoRV with low rates of KoRV induced disease. In contrast, animals in the northern part of their range universally have both endogenous and exogenous KoRV with very high rates of KoRV induced disease such as lymphoma. This paper uses a combination of sequencing technologies, Illumina RNA sequencing of “southern” (south Australian) and “northern” (SE QLD) koalas and CRISPR enrichment and nanopore sequencing of DNA of “southern” (South Australian and Victorian animals) to retrieve full length loci and intregration sites of KoRV variants. We demonstrate that koalas that tested negative to the KoRV pol gene qPCR, used to detect replication competent KoRV, are not in fact KoRV free but harbour defective, presumably endogenous, “RecKoRV” variants that are not fixed between animals. This indicates that these populations have historically been exposed to KoRV and raises questions as to whether these variants have arisen by chance or whether they provide a protective effect from the infectious forms of KoRV. This latter explanation would offer the intriguing prospect of being able to monitor and selectively breed for disease resistance to protect the wild koala population from KoRV induced disease.
Publisher: Cold Spring Harbor Laboratory
Date: 05-2023
DOI: 10.1101/2023.04.28.538769
Abstract: 2. Repeat spill over of SARS-CoV-2 into new hosts has highlighted the critical role of cross species transmission of coronaviruses and establishment of new reservoirs of virus in pandemic and epizootic spread of coronaviruses. Species particularly susceptible to SARS-CoV-2 spill-over include Mustelidae (mink, ferrets and related animals) and cricetid rodents (hamsters and related animals). These predispositions led us to screen British wildlife with sarbecovirus specific qPCR and pan coronavirus PCR assays for SARS-CoV-2 using s les collected during the human pandemic to establish if widespread spill-over was occurring. Fourteen wildlife species (n=402) were tested, including : 2 Red Foxes ( Vulpes vulpes ), 101 Badgers ( Meles meles ), 2 wild American Mink ( Neovison vison ), 41 Pine Marten ( Martes martes ), 2 Weasels ( Mustela nivalis ), 7 Stoats ( Mustela erminea ), 108 Water Voles ( Arvicola hibius ), 39 Bank voles ( Myodes glareolous ), 10 Field Voles ( Microtus agrestis ), 15 Wood Mice ( Apodemus sylvaticus ), 1 Common Shrew ( Sorex aranaeus ), 2 Pygmy Shrews ( Sorex minutus ), 2 Hedgehogs (Erinaceus europaeus ) and 75 Eurasian Otters ( Lutra lutra ). No cases of SARS-CoV-2 were detected in any animals, however a novel minacovirus related to mink and ferret alphacoronaviruses was detected in stoats recently introduced to the Orkney Islands. This group of viruses is of interest due to pathogenicity in ferrets. The impact of this virus on the health of stoat populations remains to be established.
Publisher: Australian Museum
Date: 21-06-2023
DOI: 10.3853/J.1835-4211.38.2023.1831
Abstract: Koala retrovirus (KoRV) epidemiology varies across koala (Phascolarctos cinereus) populations with distinct differences in viral prevalence, sequence ersity, and disease impact. Curiously the more genetically restricted southern populations are less impacted by KoRV with the virus not endogenized in its replication competent form in these animals. These southern animals do, however, have replication defective recKoRV variants in their genomes indicating historical exposure to KoRV and recKoRV. Whether southern animals are inherently resistant to KoRV infection and endogenization is not clear. It is also not clear whether the current regional epidemiological patterns will persist or whether exposure to animals with infectious KoRV or cross-breeding between different genetic populations will change the KoRV prevalence with time.
Publisher: Microbiology Society
Date: 14-06-2023
DOI: 10.1099/JGV.0.001859
Abstract: Horseshoe bats are the natural hosts of the Sarbecovirus subgenus that includes SARS-CoV and SARS-CoV- 2. Despite the devastating impact of the COVID-19 pandemic, there is still little known about the underlying epidemiology and virology of sarbecoviruses in their natural hosts, leaving large gaps in our pandemic preparedness. Here we describe the results of PCR testing for sarbecoviruses in the two horseshoe bat species ( Rhinolophus hipposideros and R. ferrumequinum ) present in Great Britain, collected in 2021–22 during the peak of COVID-19 pandemic. One hundred and ninety seven R. hipposideros s les from 33 roost sites and 277 R . ferrumequinum s les from 20 roost sites were tested. No coronaviruses were detected in any s les from R. ferrumequinum whereas 44 and 56 % of in idual and pooled (respectively) faecal s les from R. hipposideros across multiple roost sites tested positive in a sarbecovirus-specific qPCR. Full genome sequences were generated from three of the positive s les (and partial genomes from two more) using Illumina RNAseq on unenriched s les. Phylogenetic analyses showed that the obtained sequences belong to the same monophyletic clade, with % similarity to previously-reported European isolates from R. hipposideros . The sequences differed in the presence or absence of accessory genes ORF 7b, 9b and 10. All lacked the furin cleavage site of SARS-CoV-2 spike gene and are therefore unlikely to be infective for humans. These results demonstrate a lack, or at least low incidence, of SARS-CoV-2 spill over from humans to susceptible GB bats, and confirm that sarbecovirus infection is widespread in R. hipposideros . Despite frequently sharing roost sites with R. ferrumequinum , no evidence of cross-species transmission was found.
Publisher: Elsevier BV
Date: 09-2023
Publisher: MDPI AG
Date: 13-06-2020
DOI: 10.3390/V12060643
Abstract: Multiple sclerosis (MS) is an immune inflammatory disease, where the underlying etiological cause remains elusive. Multiple triggering factors have been suggested, including environmental, genetic and gender components. However, underlying infectious triggers to the disease are also suspected. There is an increasing abundance of evidence supporting a viral etiology to MS, including the efficacy of interferon therapy and over-detection of viral antibodies and nucleic acids when compared with healthy patients. Several viruses have been proposed as potential triggering agents, including Epstein–Barr virus, human herpesvirus 6, varicella–zoster virus, cytomegalovirus, John Cunningham virus and human endogenous retroviruses. These viruses are all near ubiquitous and have a high prevalence in adult populations (or in the case of the retroviruses are actually part of the genome). They can establish lifelong infections with periods of reactivation, which may be linked to the relapsing nature of MS. In this review, the evidence for a role for viral infection in MS will be discussed with an emphasis on immune system activation related to MS disease pathogenesis.
Publisher: SAGE Publications
Date: 27-09-2023
Publisher: Springer Science and Business Media LLC
Date: 20-02-2018
DOI: 10.1038/S41598-018-21723-0
Abstract: To better understand host and immune response to diseases, gene expression studies require identification of reference genes with stable expression for accurate normalisation. This study describes the identification and testing of reference genes with stable expression profiles in koala lymph node tissues across two genetically distinct koala populations. From the 25 most stable genes identified in transcriptome analysis, 11 genes were selected for verification using reverse transcription quantitative PCR, in addition to the commonly used ACTB and GAPDH genes. The expression data were analysed using stable genes statistical software - geNorm, BestKeeper, NormFinder, the comparative ΔCt method and RefFinder. All 13 genes showed relative stability in expression in koala lymph node tissues, however Tmem97 and Hmg20a were identified as the most stable genes across the two koala populations.
Publisher: Cold Spring Harbor Laboratory
Date: 14-02-2023
DOI: 10.1101/2023.02.14.528476
Abstract: Horseshoe bats are the natural hosts of the Sarbecovirus subgenus that includes SARS-CoV-1 and 2. Despite the devastating impacts of the COVID-19 pandemic, there is still little known about the underlying epidemiology and virology of sarbecoviruses in their natural hosts, leaving large gaps in our pandemic preparedness. Here we describe the results of PCR testing for sarbecoviruses in the two horseshoe bat species ( Rhinolophus hipposideros and R. ferrumequinum ) present in Great Britain, collected in 2021-22 during the peak of COVID-19 pandemic. One hundred and ninety seven R. hipposideros s les from 33 roost sites and 277 R. ferremequinum s les from 20 roost sites were tested. No coronaviruses were detected in any s les from R. ferrumequinum whereas 44% and 56% of in idual and pooled (respectively) faecal s les from R. hipposideros across multiple roost sites tested positive in a sarbecovirus-specific qPCR. Full genome sequences were generated from three of the positive s les (and partial genomes from two more) using Illumina RNAseq on unenriched s les. Phylogenetic analyses showed that the obtained sequences belong to the same monophyletic clade, with % similarity, as previously reported European isolates from R. hipposideros . The sequences differed in the presence or absence of accessory genes ORF 7b, 9b and 10. All lacked the furin cleavage site of SARS-CoV-2 spike gene and are therefore unlikely to be infective for humans. These results demonstrate a lack, or at least low incidence, of SARS-CoV-2 spill over from humans to susceptible GB bats, and confirm that sarbecovirus infection is widespread in R. hipposideros . Despite frequently sharing roost sites with R. ferrumequinum , no evidence of cross-species transmission was found.
Publisher: Springer Science and Business Media LLC
Date: 14-01-2020
DOI: 10.1038/S41598-019-56546-0
Abstract: Koala retrovirus (KoRV) displays features of both an endogenous and exogenous virus and is linked to neoplasia and immunosuppression in koalas. This study explores the apparent differences in the nature and impact of KoRV infection between geographically and genetically separated “northern” and “southern” koala populations, by investigating the disease status, completeness of the KoRV genome and the proviral (DNA) and viral (RNA) loads of 71 northern and 97 southern koalas. All northern animals were positive for all KoRV genes ( gag , pro-pol and env ) in both DNA and RNA forms, whereas many southern animals were missing one or more KoRV genes. There was a significant relationship between the completeness of the KoRV genome and clinical status in this population. The proviral and viral loads of the northern population were significantly higher than those of the southern population (P 0.0001), and many provirus-positive southern animals failed to express any detectable KoRV RNA. Across both populations there was a positive association between proviral load and neoplasia (P = 0.009). Potential reasons for the differences in the nature of KoRV infection between the two populations are discussed.
Publisher: Microbiology Society
Date: 10-02-2022
DOI: 10.1099/JMM.0.001506
Abstract: Maedi-visna (MV) is a lentiviral disease of sheep responsible for severe production losses in affected flocks. There are no vaccination or treatment options with control reliant on test and cull strategies. The most common diagnostic methods used at present are combination ELISAs for Gag and Env proteins with virus variability making PCR diagnostics still largely an experimental tool. To assess variability in viral loads and diagnostic tests results, serology, DNA and RNA viral loads were measured in the blood of 12 naturally infected rams repeatedly blood s led over 16 months. Six animals tested negative in one or more tests at one or more time points and would have been missed on screening programmes reliant on one test method or a single time point. In addition the one animal homozygous for the ‘K’ allele of the TMEM154 E35K SNP maintained very low viral loads in all assays and apparently cleared infection to below detectable limits at the final time point it was s led. This adds crucial data to the strong epidemiological evidence that this locus represents a genuine resistance marker for MV infection and is a strong candidate for selective breeding of sheep for resistance to disease.
Publisher: Cold Spring Harbor Laboratory
Date: 03-07-2023
DOI: 10.1101/2023.07.03.547244
Abstract: 2. Spill over of SARs-CoV-2 into a variety of wild and domestic animals has been an ongoing feature of the human pandemic. The establishment of a new reservoir in white tailed deer in North America and increasing ergence of the viruses circulating in them from those circulating in the human population has highlighted the ongoing risk this poses for global health. Some parts of the world have seen more intensive monitoring of wildlife species for SARS-CoV-2 and related coronaviruses but there are still very large gaps in geographical and species-specific information. This paper reports negative results for SARS-CoV-2 PCR based testing using a pan coronavirus end point RDRP PCR and a Sarbecovirus specific E gene qPCR on lung and or gut tissue from wildlife from the Indian State of Kerala. These animals included: 121 Rhinolophus rouxii (Rufous Horsehoe Bat), 6 Rhinolophus bedommei (Lesser Woolly Horseshoe Bat), 15 Rossettus leschenaultii (Fulvous Fruit Bat), 47 Macaca radiata (Bonnet macaques), 35 Paradoxurus hermaphroditus ( Common Palm Civet), 5 Viverricula indica (Small Indian Civet), 4 Herpestes edwardsii (Common Mongoose), 10 Panthera tigris (Bengal Tiger), 8 Panthera pardus fusca (Indian Leopard), 4 Prionailurus bengalensis (Leopard cats), 2 Felis chaus (Jungle cats), 2 Cuon alpinus (Wild dogs) and 1 Melursus ursinus (sloth bear).
Publisher: Cold Spring Harbor Laboratory
Date: 16-11-2019
DOI: 10.1101/844340
Abstract: Hantaviruses are a erse group of single-stranded, negative-sensed RNA viruses, known to cause sporadic outbreaks of potentially fatal human disease. To date, only two Orthohantavirus species have been detected in the UK - Seoul virus and Tatenale. Whilst Seoul is known to be pathogenic in humans, only partial fragments of Tatenale have been recovered, precluding any accurate analysis of its phylogeny or potential pathogenicity. To overcome this shortfall we used a degenerate primer PCR method to identify Tatenale-infection in rodents living in two separate locations in the UK. PCR positive s les were then subjected to either unbiased high-throughput sequencing or overlapping PCR product sequencing to recover the complete coding sequence of the Tatenale virus. This analysis provided in-depth insight into the evolutionary origins of this recently identified UK Orthohantavirus and unequivocally showed that Tatenale virus meets the established criteria for classification as a novel species. Crucially, our data will facilitate in vitro investigation into the zoonotic potential of Tatenale virus.
Publisher: MDPI AG
Date: 31-12-2019
DOI: 10.3390/V12010047
Abstract: The advent of unbiased metagenomic virus discovery has revolutionized studies of virus bio ersity and evolution. Despite this, our knowledge of the virosphere, including in mammalian species, remains limited. We used unbiased metagenomic sequencing to identify RNA viruses in European field voles and rabbits. Accordingly, we identified a number of novel RNA viruses including astrovirus, rotavirus A, picorna-like virus and a narmovirus (paramyxovirus). In addition, we identified a sobemovirus and a novel luteovirus that likely originated from the rabbit diet. These newly discovered viruses were often ergent from those previously described. The novel astrovirus was most closely related to a virus s led from the rodent-eating European roller bird (Coracias garrulous). PCR screening revealed that the novel narmovirus in the UK field vole had a prevalence of approximately 4%, and shared common ancestry with other rodent narmoviruses s led globally. Two novel rotavirus A sequences were detected in a UK field vole and a French rabbit, the latter with a prevalence of 5%. Finally, a highly ergent picorna-like virus found in the gut of the French rabbit virus was only ~35% similar to an arilivirus at the amino acid level, suggesting the presence of a novel viral genus within the Picornaviridae.
Publisher: Cold Spring Harbor Laboratory
Date: 07-11-2017
DOI: 10.1101/215681
Abstract: To better understand host and immune response to diseases, gene expression studies require identification of reference genes with stable expression for accurate normalisation. This study describes the selection and testing of reference genes with stable expression profiles in koala lymph node tissues across two genetically distinct koala populations. From the 25 most stable genes identified in transcriptome analysis, 11 genes were selected for verification using reverse transcription quantitative PCR, in addition to the commonly used ACTB and GAPDH genes. The expression data were analysed using stable genes statistical software - geNorm, BestKeeper, NormFinder, the comparative ΔCt method and RefFinder. All 13 genes showed relative stability in expression in koala lymph node tissues, however Tmem97 and Hmg20a were identified as the most stable genes across the two koala populations.
Publisher: Springer Science and Business Media LLC
Date: 28-11-2019
DOI: 10.1186/S12917-019-2139-7
Abstract: Schmallenberg virus (SBV) is a midge borne virus of cattle and sheep. Infection is typically asymptomatic in adult sheep but fetal infection during pregnancy can result in abortion, stillbirth, neurological disorders and malformations of variable severity in newborn animals. It was first identified in Germany and the Netherlands in 2011 and then circulated throughout Europe in 2012 and 2013. Circulation in subsequent years was low or non-existent until summer and autumn 2016, leading to an increased incidence of deformed newborn lambs and calves in 2016–17. This study reports SBV circulation in October 2016 within a group of 24 ewes and 13 rams. The ewes were monitored at 3 times points over an 11 week period (September to December 2016). Most ewes displayed an increase in SBV VNT with antibody titre increases greater in older, previously exposed ewes. Two ewes had SBV RNA detectable by RT-qPCR, one on 30/09/16 and one on 04/11/16. Of these ewes, one had detectable serum SBV RNA (indicating viraemia) despite pre-existing antibody. The rams had been previously vaccinated with a commercial inactivated SBV vaccine, they showed minimal neutralising antibody titres against SBV 8 months post-vaccination and all displayed increased titre in October 2016. This data suggests that SBV circulated for a minimum period of 5 weeks in September to October 2016 in central England. Ewes previously exposed to virus showed an enhanced antibody response compared to naïve animals. Pre-existing antibody titre did not prevent re-infection in at least one animal, implying immunity to SBV upon natural exposure may not be life-long. In addition, data suggests that immunity provided by killed adjuvanted SBV vaccines only provides short term protection ( 8 months) from virus.
Publisher: MDPI AG
Date: 30-01-2019
DOI: 10.3390/V11020125
Abstract: The recent discovery of novel alphacoronaviruses (alpha-CoVs) in European and Asian rodents revealed that rodent coronaviruses (CoVs) s led worldwide formed a discrete phylogenetic group within this genus. To determine the evolutionary history of rodent CoVs in more detail, particularly the relative frequencies of virus-host co- ergence and cross-species transmission, we recovered longer fragments of CoV genomes from previously discovered European rodent alpha-CoVs using a combination of PCR and high-throughput sequencing. Accordingly, the full genome sequence was retrieved from the UK rat coronavirus, along with partial genome sequences from the UK field vole and Poland-resident bank vole CoVs, and a short conserved ORF1b fragment from the French rabbit CoV. Genome and phylogenetic analysis showed that despite their erse geographic origins, all rodent alpha-CoVs formed a single monophyletic group and shared similar features, such as the same gene constellations, a recombinant beta-CoV spike gene, and similar core transcriptional regulatory sequences (TRS). These data suggest that all rodent alpha CoVs s led so far originate from a single common ancestor, and that there has likely been a long-term association between alpha CoVs and rodents. Despite this likely antiquity, the phylogenetic pattern of the alpha-CoVs was also suggestive of relatively frequent host-jumping among the different rodent species.
Publisher: MDPI AG
Date: 02-07-2019
DOI: 10.3390/V11070601
Abstract: Hemorrhagic fever with renal syndrome (HFRS) is endemic in Tatarstan, where thousands of cases are registered annually. Puumala orthohantavirus is commonly detected in human case s les as well as in captured bank voles, the rodent hosts. The pathogenesis of HFRS is still not well described, although the cytokine storm hypothesis is largely accepted. In this study, we present a comprehensive analysis of a fatal HFRS case compared with twenty four non-fatal cases where activation of the humoral and cellular immune responses, pro-inflammatory cytokines and disturbed blood coagulation were detected using immunological, histological, genetic and clinical approaches. Multiple organ failure combined with disseminated intravascular coagulation syndrome and acute renal failure was the cause of death. Decreased Interleukin (IL)-7 and increased IL-18, chemokine (C-C motif) ligand (CCL)-5, stem cell growth factor (SCGF)-b and tumor necrosis factor-beta (TNF-β) serum levels were found, supporting the cytokine storm hypothesis of hantavirus pathogenesis.
Publisher: Microbiology Society
Date: 11-08-2023
Abstract: Spill over of SARs-CoV-2 into a variety of wild and domestic animals has been an ongoing feature of the human pandemic. The establishment of a new reservoir in white tailed deer in North America and increasing ergence of the viruses circulating in them from those circulating in the human population has highlighted the ongoing risk this poses for global health. Some parts of the world have seen more intensive monitoring of wildlife species for SARS-CoV-2 and related coronaviruses but there are still very large gaps in geographical and species-specific information. This paper reports negative results for SARS-CoV-2 PCR based testing using a pan coronavirus end point RDRP PCR and a Sarbecovirus specific E gene qPCR on lung and or gut tissue from wildlife from the Indian State of Kerala. These animals included: 121 Rhinolophus rouxii (Rufous Horsehoe Bat), 6 Rhinolophus bedommei (Lesser Woolly Horseshoe Bat), 15 Rossettus leschenaultii (Fulvous Fruit Bat), 47 Macaca radiata (Bonnet macaques), 35 Paradoxurus hermaphroditus (Common Palm Civet), 5 Viverricula indica (Small Indian Civet) , 4 Herpestes edwardsii (Common Mongoose), 10 Panthera tigris (Bengal Tiger), 8 Panthera pardus fusca ( Indian Leopard), 4 Prionailurus bengalensis (Leopard cats), 2 Felis chaus (Jungle cats), 2 Cuon alpinus (Wild dogs) and 1 Melursus ursinus (sloth bear).
Publisher: Australian Museum
Date: 21-06-2023
DOI: 10.3853/J.1835-4211.38.2023.1842
Abstract: This document represents a synthesis of discussions held online at the Second Koala Retrovirus Workshop in 2021. The three days of discussions were based on workshop presentations and comprise: KoRV foundational science (Day 1) applied management of koalas in zoo populations (Day 2) and applied management of koalas in wild populations (Day 3). Each of these discussions gathers current knowledge, explores points of consensus and disagreement, and identifies important knowledge gaps. Recommendations arise regarding research strategy, interim measures for management, and support of research and management via initiation of working groups on KoRV diagnostics and biobanking.
Publisher: Elsevier BV
Date: 04-2020
DOI: 10.1016/J.GENE.2020.144366
Abstract: Koala retrovirus is thought to be an underlying cause of high levels of neoplasia and immunosuppression in koalas. While epidemiology studies suggest a strong link between KoRV and disease it has been difficult to prove causality because of the complex nature of the virus, which exists in both endogenous and exogenous forms. It has been difficult to identify koalas completely free of KoRV, and infection studies in koalas or koala cells are fraught with ethical and technical difficulties, respectively. This study uses KoRV infection of the susceptible human cell line HEK293T and RNAseq to demonstrate gene networks differentially regulated upon KoRV infection. Many of the pathways identified are those associated with viral infection, such as cytokine receptor interactions and interferon signalling pathways, as well as viral oncogenesis pathways. This study provides strong evidence that KoRV does indeed behave similarly to infectious retroviruses in stimulating antiviral and oncogenic cellular responses. In addition, it provides novel insights into KoRV oncogenesis with the identification of a group of histone family genes that are part of several oncogenic pathways as upregulated in KoRV infection.
Publisher: Microbiology Society
Date: 28-06-2022
DOI: 10.1099/JGV.0.001749
Abstract: Koala retrovirus (KoRV) is unique amongst endogenous (inherited) retroviruses in that its incorporation to the host genome is still active, providing an opportunity to study what drives this fundamental process in vertebrate genome evolution. Animals in the southern part of the natural range of koalas were previously thought to be either virus-free or to have only exogenous variants of KoRV with low rates of KoRV-induced disease. In contrast, animals in the northern part of their range universally have both endogenous and exogenous KoRV with very high rates of KoRV-induced disease such as lymphoma. In this study we use a combination of sequencing technologies, Illumina RNA sequencing of ‘southern’ (south Australian) and ‘northern’ (SE QLD) koalas and CRISPR enrichment and nanopore sequencing of DNA of ‘southern’ (South Australian and Victorian animals) to retrieve full-length loci and intregration sites of KoRV variants. We demonstrate that koalas that tested negative to the KoRV pol gene qPCR, used to detect replication-competent KoRV, are not in fact KoRV-free but harbour defective, presumably endogenous, ‘RecKoRV’ variants that are not fixed between animals. This indicates that these populations have historically been exposed to KoRV and raises questions as to whether these variants have arisen by chance or whether they provide a protective effect from the infectious forms of KoRV. This latter explanation would offer the intriguing prospect of being able to monitor and selectively breed for disease resistance to protect the wild koala population from KoRV-induced disease.
Publisher: Springer Science and Business Media LLC
Date: 20-02-2021
DOI: 10.1007/S10592-021-01340-7
Abstract: Historical hunting pressures on koalas in the southern part of their range in Australia have led to a marked genetic bottleneck when compared with their northern counterparts. There are a range of suspected genetic disorders such as testicular abnormalities, oxalate nephrosis and microcephaly reported at higher prevalence in these genetically restricted southern animals. This paper reports analysis of differential expression of genes from RNAseq of lymph nodes, SNPs present in genes and the fixation index (population differentiation due to genetic structure) of these SNPs from two populations, one in south east Queensland, representative of the northern genotype and one in the Mount Lofty Ranges South Australia, representative of the southern genotype. SNPs that differ between these two populations were significantly enriched in genes associated with brain diseases. Genes which were differentially expressed between the two populations included many associated with brain development or disease, and in addition a number associated with testicular development, including the androgen receptor. Finally, one of the 8 genes both differentially expressed and with a statistical difference in SNP frequency between populations was SLC26A6 (solute carrier family 26 member 6), an anion transporter that was upregulated in SA koalas and is associated with oxalate transport and calcium oxalate uroliths in humans. Together the differences in SNPs and gene expression described in this paper suggest an underlying genetic basis for several disorders commonly seen in southern Australian koalas, supporting the need for further research into the genetic basis of these conditions, and highlighting that genetic selection in managed populations may need to be considered in the future.
Publisher: Microbiology Society
Date: 09-2019
DOI: 10.1099/JGV.0.001304
Abstract: Koala retrovirus (KoRV) is a recently endogenized retrovirus associated with neoplasia and immunosuppression in koala populations. The virus is known to display sequence variability and to be present at varying prevalence in different populations, with animals in southern Australia displaying lower prevalence and viral loads than northern animals. This study used a PCR and next-generation sequencing strategy to examine the ersity of the KoRV
Location: United Kingdom of Great Britain and Northern Ireland
Location: Australia
No related grants have been discovered for Rachael Tarlinton.