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McCutcheon S.,Roslin Institute | Blanco A.R.A.,Roslin Institute | Houston E.F.,University of Glasgow | de Wolf C.,Roslin Institute | And 9 more authors.
PLoS ONE | Year: 2011

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion. © 2011 McCutcheon et al.


PubMed | Masaryk University, Slovak Academy of Sciences, Veterinary Research Institute, Institute for Novel and Emerging Infectious Diseases and 2 more.
Type: | Journal: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases | Year: 2016

Hantaviruses are emerging RNA viruses that cause human diseases predominantly in Asia, Europe, and the Americas. Besides rodents, insectivores and bats serve as hantavirus reservoirs. We report the detection and genome characterization of a novel bat-borne hantavirus isolated from insectivorous common noctule bat. The newfound virus was tentatively named as Brno virus.


Eiden M.,Institute for Novel and Emerging Infectious Diseases | Hoffmann C.,Institute for Novel and Emerging Infectious Diseases | Balkema-Buschmann A.,Institute for Novel and Emerging Infectious Diseases | Muller M.,Bayerisches Landesamt fur Gesundheit und Lebensmittelsicherheit | And 2 more authors.
Journal of General Virology | Year: 2010

Feline spongiform encephalopathy (FSE) is a transmissible spongiform encephalopathy that affects domestic cats (Felis catus) and captive wild members of the family Felidae. In this report we describe a case of FSE in a captive cheetah from the zoological garden of Nuremberg. The biochemical examination revealed a BSE-like pattern. Disease-associated scrapie prion protein (PrP Sc) was widely distributed in the central and peripheral nervous system, as well as in the lymphoreticular system and in other tissues of the affected animal, as demonstrated by immunohistochemistry and/or immunoblotting. Moreover, we report for the first time the use of the protein misfolding cyclic amplification technique for highly sensitive detection of PrPSc in the family Felidae. The widespread PrPSc deposition suggests a simultaneous lymphatic and neural spread of the FSE agent. The detection of PrPSc in the spleen indicates a potential for prion infectivity of cheetah blood. © 2010 SGM.


Seldin M.M.,Johns Hopkins University | Byerly M.S.,Johns Hopkins University | Petersen P.S.,Johns Hopkins University | Swanson R.,Johns Hopkins University | And 3 more authors.
Journal of Experimental Biology | Year: 2014

Mammalian hibernation elicits profound changes in whole-body physiology. The liver-derived hibernation protein (HP) complex, consisting of HP-20, HP-25 and HP-27, was shown to oscillate circannually, and this oscillation in the central nervous system (CNS) was suggested to play a role in hibernation. The HP complex has been found in hibernating chipmunks but not in related nonhibernating tree squirrels, leading to the suggestion that hibernationspecific genes may underlie the origin of hibernation. Here, we show that non-hibernating mammals express and regulate the conserved homologous HP complex in a seasonal manner, independent of hibernation. Comparative analyses of cow and chipmunk HPs revealed extensive biochemical and structural conservations. These include liver-specific expression, assembly of distinct heteromeric complexes that circulate in the blood and cerebrospinal fluid, and the striking seasonal oscillation of the HP levels in the blood and CNS. Central administration of recombinant HPs affected food intake in mice, without altering body temperature, physical activity levels or energy expenditure. Our results demonstrate that HP complex is not unique to the hibernators and suggest that the HP-regulated liver-brain circuit may couple seasonal changes in the environment to alterations in physiology. © 2014. Published by The Company of Biologists Ltd.


Jahns H.,University College Dublin | Fast C.,Institute for Novel and Emerging Infectious Diseases
Journal of Comparative Pathology | Year: 2014

One hundred and sixty-eight ganglia from 54 cattle aged 10 days to 10 years were examined microscopically. Samples from six autonomic ganglia and one sensory ganglion were represented. Thirteen animals were clinically normal and 41 were submitted for post-mortem examination. Neuronal vacuolation, spheroid formation, lipofuscin accumulation and central chromatolysis were observed sporadically and were of varying magnitude. Neuronal vacuolation and spheroid formation were not age-related changes, while lipofuscin accumulation was more common in older animals and central chromatolysis was more common in younger cattle. Non-suppurative inflammation and neuronophagia were also common findings (23 out of 54 animals, 42.6%) in autonomic ganglia that did not contain herpesvirus DNA as determined by polymerase chain reaction. Renaut bodies, features of peripheral nerves, were most commonly noted in the vagus. None of the histopathological findings were related to any particular disease in which loss of autonomic nervous system function might be expected. Furthermore, all changes were as common in clinically normal animals as in animals with disease. © 2013 Elsevier Ltd.


PubMed | Free University of Berlin, Institute for Novel and Emerging Infectious Diseases, University of Tromsø, Robert Koch Institute and 2 more.
Type: Journal Article | Journal: PloS one | Year: 2016

Horizontal gene transfer (HGT) is an important driver for resistance- and virulence factor accumulation in pathogenic bacteria such as Staphylococcus aureus.Here, we have investigated the downstream region of the bacterial chromosomal attachment site (attB) for the staphylococcal cassette chromosome mec (SCCmec) element of a commensal mecC-positive Staphylococcus stepanovicii strain (IMT28705; ODD4) with respect to genetic composition and indications of HGT. S. stepanovicii IMT28705 was isolated from a fecal sample of a trapped wild bank vole (Myodes glareolus) during a screening study (National Network on Rodent-Borne Pathogens) in Germany. Whole genome sequencing (WGS) of IMT28705 together with the mecC-negative type strain CM7717 was conducted in order to comparatively investigate the genomic region downstream of attB (GenBank accession no. KR732654 and KR732653).The bank vole isolate (IMT28705) harbors a mecC gene which shares 99.2% nucleotide (and 98.5% amino acid) sequence identity with mecC of MRSA_LGA251. In addition, the mecC-encoding region harbors the typical blaZ-mecC-mecR1-mecI structure, corresponding with the class E mec complex. While the sequences downstream of attB in both S. stepanovicii isolates (IMT28705 and CM7717) are partitioned by 15 bp direct repeats, further comparison revealed a remarkable low concordance of gene content, indicating a chromosomal hot spot for foreign DNA integration and exchange.Our data highlight the necessity for further research on transmission routes of resistance encoding factors from the environmental and wildlife resistome.


Kaatz M.,Institute for Novel and Emerging Infectious Diseases | Fast C.,Institute for Novel and Emerging Infectious Diseases | Ziegler U.,Institute for Novel and Emerging Infectious Diseases | Balkema-Buschmann A.,Institute for Novel and Emerging Infectious Diseases | And 5 more authors.
American Journal of Pathology | Year: 2012

An experimental oral bovine spongiform encephalopathy (BSE) challenge study was performed to elucidate the route of infectious prions from the gut to the central nervous system in preclinical and clinical infected animals. Tissue samples collected from the gut and the central and autonomic nervous system from animals sacrificed between 16 and 44 months post infection (mpi) were examined for the presence of the pathological prion protein (PrPSc) by IHC. Moreover, parts of these samples were also bioassayed using bovine cellular prion protein (PrPC) overexpressing transgenic mice (Tgbov XV) that lack the species barrier for bovine prions. A distinct accumulation of PrP Sc was observed in the distal ileum, confined to follicles and/or the enteric nervous system, in almost all animals. BSE prions were found in the sympathetic nervous system starting at 16 mpi, and in the parasympathetic nervous system from 20 mpi. A clear dissociation between prion infectivity and detectable PrPSc deposition became obvious. The earliest presence of infectivity in the brain stem was detected at 24 mpi, whereas PrPSc accumulation was first detected after 28 mpi. In summary, our results decipher the centripetal spread of BSE prions along the autonomic nervous system to the central nervous system, starting already halfway in the incubation time. © 2012 American Society for Investigative Pathology.


Eckerle I.,University of Bonn | Lenk M.,Friedrich Loeffler Institute | Ulrich R.G.,Institute for Novel and Emerging Infectious Diseases
Viruses | Year: 2014

Due to novel, improved and high-throughput detection methods, there is a plethora of newly identified viruses within the genus Hantavirus. Furthermore, reservoir host species are increasingly recognized besides representatives of the order Rodentia, now including members of the mammalian orders Soricomorpha/Eulipotyphla and Chiroptera. Despite the great interest created by emerging zoonotic viruses, there is still a gross lack of in vitro models, which reflect the exclusive host adaptation of most zoonotic viruses. The usually narrow host range and genetic diversity of hantaviruses make them an exciting candidate for studying virus-host interactions on a cellular level. To do so, well-characterized reservoir cell lines covering a wide range of bat, insectivore and rodent species are essential. Most currently available cell culture models display a heterologous virus-host relationship and are therefore only of limited value. Here, we review the recently established approaches to generate reservoir-derived cell culture models for the in vitro study of virus-host interactions. These successfully used model systems almost exclusively originate from bats and bat-borne viruses other than hantaviruses. Therefore we propose a parallel approach for research on rodent- and insectivore-borne hantaviruses, taking the generation of novel rodent and insectivore cell lines from wildlife species into account. These cell lines would be also valuable for studies on further rodent-borne viruses, such as orthopox- and arenaviruses. © 2014 by the authors; licensee MDPI, Basel, Switzerland.


Schlosser J.,Institute for Novel and Emerging Infectious Diseases | Eiden M.,Institute for Novel and Emerging Infectious Diseases | Vina-Rodriguez A.,Institute for Novel and Emerging Infectious Diseases | Fast C.,Institute for Novel and Emerging Infectious Diseases | And 4 more authors.
Veterinary Research | Year: 2014

Hepatitis E virus (HEV) is the causative agent of acute hepatitis E in humans in developing countries, but sporadic and autochthonous cases do also occur in industrialised countries. In Europe, food-borne zoonotic transmission of genotype 3 (gt3) has been associated with domestic pig and wild boar. However, little is known about the course of HEV infection in European wild boar and their role in HEV transmission to domestic pigs. To investigate the transmissibility and pathogenesis of wild boar-derived HEVgt3, we inoculated four wild boar and four miniature pigs intravenously. Using quantitative real-time RT-PCR viral RNA was detected in serum, faeces and in liver, spleen and lymph nodes. The antibody response evolved after fourteen days post inoculation. Histopathological findings included mild to moderate lymphoplasmacytic hepatitis which was more prominent in wild boar than in miniature pigs. By immunohistochemical methods, viral antigens were detected mainly in Kupffer cells and liver sinusoidal endothelial cells, partially associated with hepatic lesions, but also in spleen and lymph nodes. While clinical symptoms were subtle and gross pathology was inconspicuous, increased liver enzyme levels in serum indicated hepatocellular injury. As the faecal-oral route is supposed to be the most likely transmission route, we included four contact animals to prove horizontal transmission. Interestingly, HEVgt3-infection was also detected in wild boar and miniature pigs kept in contact to intravenously inoculated wild boar. Given the high virus loads and long duration of viral shedding, wild boar has to be considered as an important HEV reservoir and transmission host in Europe. © 2014 Schlosser et al.; licensee BioMed Central Ltd.


Vina-Rodriguez A.,Institute for Novel and Emerging Infectious Diseases | Schlosser J.,Institute for Novel and Emerging Infectious Diseases | Becher D.,Micromun GmbH Greifswald | Kaden V.,Institute of Infectology | And 2 more authors.
Viruses | Year: 2015

An increasing number of indigenous cases of hepatitis E caused by genotype 3 viruses (HEV-3) have been diagnosed all around the word, particularly in industrialized countries. Hepatitis E is a zoonotic disease and accumulating evidence indicates that domestic pigs and wild boars are the main reservoirs of HEV-3. A detailed analysis of HEV-3 subtypes could help to determine the interplay of human activity, the role of animals as reservoirs and cross species transmission. Although complete genome sequences are most appropriate for HEV subtype determination, in most cases only partial genomic sequences are available. We therefore carried out a subtype classification analysis, which uses regions from all three open reading frames of the genome. Using this approach, more than 1000 published HEV-3 isolates were subtyped. Newly recovered HEV partial sequences from hunted German wild boars were also included in this study. These sequences were assigned to genotype 3 and clustered within subtype 3a, 3i and, unexpectedly, one of them within the subtype 3b, a first non-human report of this subtype in Europe. © 2015 by the authors; licensee MDPI, Basel, Switzerland.

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