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3. The attenuated Rift Valley fever virus strain clone 13 induces encephalitis in type 1 interferon competent mice

Author

Michaely, L.M., primary, Schuwerk, L., additional, Allnoch, L., additional, Schön, K., additional, Waltl, I., additional, Larsen, P.K., additional, Pavlou, A., additional, Prajeeth, C.K., additional, Rimmelzwaan, G.F., additional, Becker, S.C., additional, Kalinke, U., additional, Baumgärtner, W., additional, and Gerhauser, I., additional

Published
2023
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4. Retinal pathology in COVID-19: will animal models help us?

Author

Gregor, K.M., primary, Ciurkiewicz, M., additional, Rosiak, M., additional, Volz, A., additional, Allnoch, L., additional, Clever, S., additional, Zu Natrup, C. Meyer, additional, Schünemann, L.M., additional, Armando, F., additional, Gerhauser, I., additional, Becker, K., additional, Beythien, G., additional, Gabriel, G., additional, Schulz, C., additional, von Köckritz-Blickwede, M., additional, and Baumgärtner, W., additional

Published
2023
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13. Canine dorsal root ganglia satellite glial cells represent an exceptional cell population with astrocytic and oligodendrocytic properties

Author

Tongtako, W., Lehmbecker, A., Wang, Y., Hahn, K., Baumgärtner, W., and Gerhauser, I.

Subjects
Mice, Oligodendroglia, Dogs, nervous system, Astrocytes, Ganglia, Spinal, lcsh:R, Animals, lcsh:Medicine, lcsh:Q, lcsh:Science, Article
Abstract

Dogs can be used as a translational animal model to close the gap between basic discoveries in rodents and clinical trials in humans. The present study compared the species-specific properties of satellite glial cells (SGCs) of canine and murine dorsal root ganglia (DRG) in situ and in vitro using light microscopy, electron microscopy, and immunostainings. The in situ expression of CNPase, GFAP, and glutamine synthetase (GS) has also been investigated in simian SGCs. In situ, most canine SGCs (>80%) expressed the neural progenitor cell markers nestin and Sox2. CNPase and GFAP were found in most canine and simian but not murine SGCs. GS was detected in 94% of simian and 71% of murine SGCs, whereas only 44% of canine SGCs expressed GS. In vitro, most canine (>84%) and murine (>96%) SGCs expressed CNPase, whereas GFAP expression was differentially affected by culture conditions and varied between 10% and 40%. However, GFAP expression was induced by bone morphogenetic protein 4 in SGCs of both species. Interestingly, canine SGCs also stimulated neurite formation of DRG neurons. These findings indicate that SGCs represent an exceptional, intermediate glial cell population with phenotypical characteristics of oligodendrocytes and astrocytes and might possess intrinsic regenerative capabilities in vivo.

Published
2017

15. Inhibition of caspase-1 prolongs survival of mice infected with rabies virus

Author

Koraka, Penelopie, Martina, Byron, Smreczak, M, Orlowska, A, Marzec, A, Trebas, P, Roose, Jeroen, Begeman, Lineke, Gerhauser, I, Wohlsein, P, Baumgartner, W, Zmudzinski, J, Osterhaus, A, Koraka, Penelopie, Martina, Byron, Smreczak, M, Orlowska, A, Marzec, A, Trebas, P, Roose, Jeroen, Begeman, Lineke, Gerhauser, I, Wohlsein, P, Baumgartner, W, Zmudzinski, J, and Osterhaus, A

Published
2019

23. Combination drug treatment prolongs survival of experimentally infected mice with silver-haired bat rabies virus

Author

Martina, B.E.E. (Byron), Smreczak, M. (Marcin), Orlowska, A. (Anna), Marzec, A. (Anna), Trebas, P. (Pawel), Roose, J.M. (Jouke M.), Zmudzinski, J. (Jan), Gerhauser, I. (Ingo), Wohlsein, P. (Peter), Baumgärtner, V. (Volkmar), Osterhaus, A.D.M.E. (Albert), Koraka, P. (Penelope), Martina, B.E.E. (Byron), Smreczak, M. (Marcin), Orlowska, A. (Anna), Marzec, A. (Anna), Trebas, P. (Pawel), Roose, J.M. (Jouke M.), Zmudzinski, J. (Jan), Gerhauser, I. (Ingo), Wohlsein, P. (Peter), Baumgärtner, V. (Volkmar), Osterhaus, A.D.M.E. (Albert), and Koraka, P. (Penelope)

Abstract

Rabies is a lethal disease in humans and animals, killing approximately 60,000 people every year. Currently, there is no treatment available, except post-exposure prophylaxis (PEP) that can be administered whenever exposure to a rabid animal took place. Here we describe the beneficial effects of a combination treatment initiated at

Published
2018
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24. Inhibition of caspase-1 prolongs survival of mice infected with rabies virus

Author

Koraka, P. (Penelope), Martina, B.E.E. (Byron), Smreczak, M. (Marcin), Orlowska, A. (Anna), Marzec, A. (Anna), Trebas, P. (Pawel), Roose, J.M. (Jouke M.), Begeman, L. (Lineke), Gerhauser, I. (Ingo), Wohlsein, P. (Peter), Baumgärtner, V. (Volkmar), Zmudzinski, J. (Jan), D.M.E. Osterhaus, A. (Albert), Koraka, P. (Penelope), Martina, B.E.E. (Byron), Smreczak, M. (Marcin), Orlowska, A. (Anna), Marzec, A. (Anna), Trebas, P. (Pawel), Roose, J.M. (Jouke M.), Begeman, L. (Lineke), Gerhauser, I. (Ingo), Wohlsein, P. (Peter), Baumgärtner, V. (Volkmar), Zmudzinski, J. (Jan), and D.M.E. Osterhaus, A. (Albert)

Abstract

Rabies virus infects almost all mammals resulting in lethal disease. To date there is no treatment available for symptomatic rabies and there is an urgent need to develop treatment strategies that would prolong survival, thereby providing a window of opportunity for the host to mount a protective immune response. We hypothesized that both virus and excessive immune response contribute to disease and that interfering with both is necessary to prevent lethal disease. Here, we have inhibited the pro-inflammatory response associated with pyroptosis and showed that inhibition of CASP-1 had a beneficial effect on survival time. Our results confirm that some inflammatory responses may be involved in the pathogenesis of severe disease and the results suggest that effective intervention includes inhibition of virus and host response.

Published
2018
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32. Pathologie der Retina bei COVID-19 Tiermodellen

Author

Gregor, K M, Rosiak, M, Beythien, G, Allnoch, L, Clever, S, Meyer zu Natrup, C, Schünemann, L-M, Becker, K, Armando, F, Gerhauser, I, Bleyer, M, Gruber-Dujardin, E, Mätz-Rensing, K, Pöhlmann, S, Osterhaus, ADM E, Gabriel, G, Schulz, C, von Köckritz-Blickwede, M, Volz, A, Baumgärtner, W, and Ciurkiewicz, M

Published
2023
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35. Pathologie der Retina bei COVID-19 Tiermodellen

Author

Gregor, K. M., Rosiak, M., Beythien, G., Allnoch, L., Clever, S., Meyer zu Natrup, C., Schünemann, L.-M., Becker, K., Armando, F., Gerhauser, I., Bleyer, M., Gruber- Dujardin, E., Mätz-Rensing, K., Pöhlmann, S., Osterhaus, A.D.M. E., Gabriel, G., Schulz, C., von Köckritz-Blickwede, M., Volz, A., Baumgärtner, W., and Ciurkiewicz, M.

Published
2023
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44. Two New Cases of Polysomy 13 in Canine Prostate Cancer.

Author

Reimann-Berg, N., Willenbrock, S., Murua Escobar, H., Eberle, N., Gerhauser, I., Mischke, R., Bullerdiek, J., and Nolte, I.

Subjects
ANIMAL models of prostate cancer, CANCER in animals, LABORATORY dogs, CHROMOSOME abnormalities, CYTOGENETICS, KARYOTYPES
Abstract

Besides man, the dog is the only known mammalian species that spontaneously develops carcinomas of the prostate with considerable frequency. For this reason, the dog is considered to be the only useful animal model for spontaneously occurring prostate malignancies in man. Cytogenetic investigations of human prostate cancers have revealed the frequent occurrence of trisomies 7, 8, and 17. Chromosome analyses of canine prostate carcinomas are rare. In this report we present 2 cases of canine prostate cancer showing a clonal polysomy 13 along with complex karyotype changes. Along with a previous report demonstrating polysomy 13 as the only karyotype deviation in a canine prostate cancer the present report supports the hypothesis that in canine prostate cancer, polysomy 13 is a recurrent cytogenetic aberration linked to the development of the disease. As human chromosomes (HSA) 8q and 4q and the canine chromosome (CFA) 13 share high homology, these results suggest that a conserved area on these chromosomes is involved in tumorigenesis in both species. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Published
2010
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49. A multiantigenic Orf virus-based vaccine efficiently protects hamsters and nonhuman primates against SARS-CoV-2.

Author

Reguzova A, Müller M, Pagallies F, Burri D, Salomon F, Rziha HJ, Bittner-Schrader Z, Verstrepen BE, Böszörményi KP, Verschoor EJ, Gerhauser I, Elbers K, Esen M, Manenti A, Monti M, Rammensee HG, Derouazi M, Löffler MW, and Amann R

Abstract

Among the common strategies to design next-generation COVID-19 vaccines is broadening the antigenic repertoire thereby aiming to increase efficacy against emerging variants of concern (VoC). This study describes a new Orf virus-based vector (ORFV) platform to design a multiantigenic vaccine targeting SARS-CoV-2 spike and nucleocapsid antigens. Vaccine candidates were engineered, either expressing spike protein (ORFV-S) alone or co-expressing nucleocapsid protein (ORFV-S/N). Mono- and multiantigenic vaccines elicited comparable levels of spike-specific antibodies and virus neutralization in mice. Results from a SARS-CoV-2 challenge model in hamsters suggest cross-protective properties of the multiantigenic vaccine against VoC, indicating improved viral clearance with ORFV-S/N, as compared to equal doses of ORFV-S. In a nonhuman primate challenge model, vaccination with the ORFV-S/N vaccine resulted in long-term protection against SARS-CoV-2 infection. These results demonstrate the potential of the ORFV platform for prophylactic vaccination and represent a preclinical development program supporting first-in-man studies with the multiantigenic ORFV vaccine., (© 2024. The Author(s).)

Published
2024
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50. A New Methodology for the Oxygen Measurement in Lung Tissue of an Aged Ferret Model Proves Hypoxia during COVID-19.

Author

Wirz K, Schulz C, Söbbeler F, Armando F, Beythien G, Gerhauser I, de Buhr N, Pilchová V, Meyer Zu Natrup C, Baumgärtner W, Kästner S, and von Köckritz-Blickwede M

Subjects
Animals, Male, Female, Ferrets, COVID-19 metabolism, COVID-19 virology, Oxygen metabolism, Lung metabolism, Lung virology, Lung pathology, SARS-CoV-2, Disease Models, Animal, Hypoxia metabolism, Hypoxia virology
Abstract

Oxygen as a key element has a high impact on cellular processes. Infection with a pathogen such as SARS-CoV-2 and after inflammation may lead to hypoxic conditions in tissue that impact cellular responses. To develop optimized translational in vitro models for a better understanding of physiologic and pathophysiologic oxygen conditions, it is a prerequisite to determine oxygen concentrations generated in vivo . Our study objective was the establishment of an invasive method for oxygen measurements using a luminescence-based microsensor to determine the dissolved oxygen in the lung tissue of ferrets as animal models for SARS-CoV-2 research. By way of analogy to humans, aged ferrets are more likely to show clinical signs after SARS-CoV-2 infection than are young animals. To investigate oxygen concentrations during a respiratory viral infection, we intratracheally infected nine aged (3-yr-old) ferrets with SARS-CoV-2. The aged SARS-CoV-2-infected ferrets showed mild to moderate clinical signs associated with prolonged viral RNA shedding until 14 days postinfection. SARS-CoV-2-infected ferrets showed histopathologic lung lesion scores that significantly negatively correlated with oxygen concentrations in lung tissue. At 4 days postinfection, oxygen concentrations in lung tissue were significantly lower (mean percentage O 2 , 3.89 ≙ ≈ 27.78 mm Hg) than in the negative control group (mean percentage O 2 , 8.65 ≙ ≈ 61.4 mm Hg). In summary, we succeeded in determining the pathophysiologic oxygen conditions in the lung tissue of aged SARS-CoV-2-infected ferrets.

Published
2024
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