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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. Source

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. Source

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 | Groschup M.H.,Institute for Novel and Emerging Infectious Diseases
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. Source

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. Source

Leidel F.,Institute for Novel and Emerging Infectious Diseases | Eiden M.,Institute for Novel and Emerging Infectious Diseases | Geissen M.,Institute for Novel and Emerging Infectious Diseases | Kretzschmar H.A.,Ludwig Maximilians University of Munich | And 5 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011

Transmissible spongiform encephalopathies (TSEs) represent a group of fatal neurodegenerative disorders that can be transmitted by natural infection or inoculation. TSEs include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, and Creutzfeldt-Jakob disease (CJD) in humans. The emergence of a variant form of CJD (vCJD), which has been associated with BSE, produced strong pressure to search for effective treatments with new drugs. Up to now, however, TSEs have proved incurable, although many efforts have been made both in vitro and in vivo to search for potent therapeutic and prophylactic compounds. For this purpose, we analyzed a compound library consisting of 10,000 compounds with a cell-based high-throughput screening assay dealing with scrapie-infected scrapie mouse brain and ScN 2A cells and identified a new class of inhibitors consisting of 3,5-diphenylpyrazole (DPP) derivatives. The most effective DPP derivative showed half-maximal inhibition of PrP Sc formation at concentrations (IC 50) of 0.6 and 1.2 μM, respectively. This compound was subsequently subjected to a number of animal experiments using scrapie-infected wild-type C57BL/6 and transgenic Tga20 mice. The DPP derivative induced a significant increase of incubation time both in therapeutic and prophylactic experiments. The onset of the prion disease was delayed by 37 days after intraperitoneal and 42 days after oral application, respectively. In summary, we demonstrate a high in vitro efficiency of DPP derivatives against prion infections that was substantiated in vivo for one of these compounds. These results indicate that the novel class of DPP compounds should comprise excellent candidates for future therapeutic studies. Copyright © 2011, American Society for Microbiology. Source

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