240 results on '"Christian Grund"'
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2. Immune response after oral immunization of goats and foxes with an NDV vectored rabies vaccine candidate.
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Magdalena Murr, Conrad Freuling, David Pérez-Bravo, Christian Grund, Thomas C Mettenleiter, Angela Römer-Oberdörfer, Thomas Müller, and Stefan Finke
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Vaccination of the reservoir species is a key component in the global fight against rabies. For wildlife reservoir species and hard to reach spillover species (e. g. ruminant farm animals), oral vaccination is the only solution. In search for a novel potent and safe oral rabies vaccine, we generated a recombinant vector virus based on lentogenic Newcastle disease virus (NDV) strain Clone 30 that expresses the glycoprotein G of rabies virus (RABV) vaccine strain SAD L16 (rNDV_GRABV). Transgene expression and virus replication was verified in avian and mammalian cells. To test immunogenicity and viral shedding, in a proof-of-concept study six goats and foxes, representing herbivore and carnivore species susceptible to rabies, each received a single dose of rNDV_GRABV (108.5 TCID50/animal) by direct oral application. For comparison, three animals received the similar dose of the empty viral vector (rNDV). All animals remained clinically inconspicuous during the trial. Viral RNA could be isolated from oral and nasal swabs until four (goats) or seven days (foxes) post vaccination, while infectious NDV could not be re-isolated. After four weeks, three out of six rNDV_GRABV vaccinated foxes developed RABV binding and virus neutralizing antibodies. Five out of six rNDV_GRABV vaccinated goats displayed RABV G specific antibodies either detected by ELISA or RFFIT. Additionally, NDV and RABV specific T cell activity was demonstrated in some of the vaccinated animals by detecting antigen specific interferon γ secretion in lymphocytes isolated from pharyngeal lymph nodes. In conclusion, the NDV vectored rabies vaccine rNDV_GRABV was safe and immunogenic after a single oral application in goats and foxes, and highlight the potential of NDV as vector for oral vaccines in mammals.
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- 2024
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3. Evaluation of SARS-CoV-2-Specific IgY Antibodies: Production, Reactivity, and Neutralizing Capability against Virus Variants
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Jacob Schön, Andrea Aebischer, Nico Joël Halwe, Lorenz Ulrich, Donata Hoffmann, Sven Reiche, Martin Beer, and Christian Grund
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antibodies ,SARS-CoV-2 ,IgY ,yolk ,lumazine synthase ,SpyTag/SpyCatcher ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
The emergence of SARS-CoV-2 in late 2019 initiated a global pandemic, which led to a need for effective therapeutics and diagnostic tools, including virus-specific antibodies. Here, we investigate different antigen preparations to produce SARS-CoV-2-specific and virus-neutralizing antibodies in chickens (n = 3/antigen) and rabbits (n = 2/antigen), exploring, in particular, egg yolk for large-scale production of immunoglobulin Y (IgY). Reactivity profiles of IgY preparations from chicken sera and yolk and rabbit sera were tested in parallel. We compared three types of antigens based on ancestral SARS-CoV-2: an inactivated whole-virus preparation, an S1 spike-protein subunit (S1 antigen) and a receptor-binding domain (RBD antigen, amino acids 319–519) coated on lumazine synthase (LS) particles using SpyCather/SpyTag technology. The RBD antigen proved to be the most efficient immunogen, and the resulting chicken IgY antibodies derived from serum or yolk, displayed strong reactivity with ELISA and indirect immunofluorescence and broad neutralizing activity against SARS-CoV-2 variants, including Omicron BA.1 and BA.5. Preliminary in vivo studies using RBD–lumazine synthase yolk preparations in a hamster model showed that local application was well tolerated and not harmful. However, despite the in vitro neutralizing capacity, this antibody preparation did not show protective effect. Further studies on galenic properties seem to be necessary. The RBD–lumazine antigen proved to be suitable for producing SARS-CoV-2 specific antibodies that can be applied to such therapeutic approaches and as reference reagents for SARS-CoV-2 diagnostics, including virus neutralization assays.
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- 2024
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4. Low Susceptibility of Pigs against Experimental Infection with HPAI Virus H5N1 Clade 2.3.4.4b
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Annika Graaf, Ronja Piesche, Julia Sehl-Ewert, Christian Grund, Anne Pohlmann, Martin Beer, and Timm Harder
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pigs ,HPAIV ,H5N1 ,zoonosis ,mammal ,panzootic ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
We found that nasal and alimentary experimental exposure of pigs to highly pathogenic avian influenza virus H5N1 clade 2.3.4.4b was associated with marginal viral replication, without inducing any clinical manifestation or pathological changes. Only 1 of 8 pigs seroconverted, pointing to high resistance of pigs to clade 2.3.4.4b infection.
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- 2023
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5. Has Epizootic Become Enzootic? Evidence for a Fundamental Change in the Infection Dynamics of Highly Pathogenic Avian Influenza in Europe, 2021
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Anne Pohlmann, Jacqueline King, Alice Fusaro, Bianca Zecchin, Ashley C. Banyard, Ian H. Brown, Alexander M. P. Byrne, Nancy Beerens, Yuan Liang, Rene Heutink, Frank Harders, Joe James, Scott M. Reid, Rowena D. E. Hansen, Nicola S. Lewis, Charlotte Hjulsager, Lars E. Larsen, Siamak Zohari, Kristofer Anderson, Caroline Bröjer, Alexander Nagy, Vladimir Savič, Steven van Borm, Mieke Steensels, Francois-Xavier Briand, Edyta Swieton, Krzysztof Smietanka, Christian Grund, Martin Beer, and Timm Harder
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high-pathogenicity avian influenza ,migratory birds ,poultry ,enzootic ,evolution ,Europe ,Microbiology ,QR1-502 - Abstract
ABSTRACT Phylogenetic evidence from the recent resurgence of high-pathogenicity avian influenza (HPAI) virus subtype H5N1, clade 2.3.4.4b, observed in European wild birds and poultry since October 2021, suggests at least two different and distinct reservoirs. We propose contrasting hypotheses for this emergence: (i) resident viruses have been maintained, presumably in wild birds, in northern Europe throughout the summer of 2021 to cause some of the outbreaks that are part of the most recent autumn/winter 2021 epizootic, or (ii) further virus variants were reintroduced by migratory birds, and these two sources of reintroduction have driven the HPAI resurgence. Viruses from these two principal sources can be distinguished by their hemagglutinin genes, which segregate into two distinct sublineages (termed B1 and B2) within clade 2.3.4.4b, as well as their different internal gene compositions. The evidence of enzootic HPAI virus circulation during the summer of 2021 indicates a possible paradigm shift in the epidemiology of HPAI in Europe.
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- 2022
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6. Monoclonal antibodies specific for the hemagglutinin-neuraminidase protein define neutralizing epitopes specific for Newcastle disease virus genotype 2.VII from Egypt
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Ibrahim Moharam, Olayinka Asala, Sven Reiche, Hafez Hafez, Martin Beer, Timm Harder, and Christian Grund
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Monoclonal antibody ,Newcastle disease virus ,Genotype 2.VII ,Antigenicity ,Hemagglutinin-Neuraminidase protein ,Conformational epitopes ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Newcastle disease is a devastating disease in poultry caused by virulent Newcastle disease virus (NDV), a paramyxovirus endemic in many regions of the world despite intensive vaccination. Phylogenetic analyses reveal ongoing evolution of the predominant circulating genotype 2.VII, and the relevance of potential antigenic drift is under discussion. To investigate variation within neutralization-sensitive epitopes within the protein responsible for receptor binding, i.e. the Hemagglutinin-Neuraminidase (HN) spike protein, we were interested in establishing genotype-specific monoclonal antibodies (MAbs). Methods An HN-enriched fraction of a gradient-purified NDV genotype 2.VII was prepared and successfully employed to induce antibodies in BalbC mice that recognize conformationally intact sites reactive by haemagglutination inhibition (HI). For subsequent screening of mouse hybridoma cultures, an NDV-ELISA was established that utilizes Concanavalin A (ConA-ELISA) coupled glycoproteins proven to present conformation-dependent epitopes. Results Six out of nine selected MAbs were able to block receptor binding as demonstrated by HI activity. One MAb recognized an epitope only present in the homologue virus, while four other MAbs showed weak reactivity to selected other genotypes. On the other hand, one broadly cross-reacting MAb reacted with all genotypes tested and resembled the reactivity profile of genotype-specific polyclonal antibody preparations that point to minor antigenic differences between tested NDV genotpyes. Conclusions These results point to the concurrent presence of variable and conserved epitopes within the HN molecule of NDV. The described protocol should help to generate MAbs against a variety of NDV strains and to enable in depth analysis of the antigenic profiles of different genotypes.
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- 2021
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7. Emergence and spread of novel H5N8, H5N5 and H5N1 clade 2.3.4.4 highly pathogenic avian influenza in 2020
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Nicola S. Lewis, Ashley C. Banyard, Elliot Whittard, Talgat Karibayev, Thamer Al Kafagi, Ilya Chvala, Alex Byrne, Saduakassova Meruyert (Akberovna), Jacqueline King, Timm Harder, Christian Grund, Steve Essen, Scott M. Reid, Adam Brouwer, Nikolay G. Zinyakov, Azimkhan Tegzhanov, Victor Irza, Anne Pohlmann, Martin Beer, Ron A. M. Fouchier, Sultanov Akhmetzhan (Akievich), and Ian H. Brown
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Influenza ,emergence ,HPAI ,Eurasia ,avian ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
Analyses of HPAI H5 viruses from poultry outbreaks across a wide Eurasian region since July 2020 including the Russian Federation, Republics of Iraq and Kazakhstan, and recent detections in migratory waterfowl in the Netherlands, revealed undetected maintenance of H5N8, likely in galliform poultry since 2017/18 and both H5N5 and H5N1. All viruses belong to A/H5 clade 2.3.4.4b with closely related HA genes. Heterogeneity in Eurasian H5Nx HPAI emerging variants threatens poultry production, food security and veterinary public health.
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- 2021
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8. Comparison of pathogenicity of subtype H9 avian influenza wild-type viruses from a wide geographic origin expressing mono-, di-, or tri-basic hemagglutinin cleavage sites
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Rokshana Parvin, Jan Schinkoethe, Christian Grund, Reiner Ulrich, Franziska Bönte, Klaus P. Behr, Matthias Voss, Mohammed A. Samad, Kareem E. Hassan, Christine Luttermann, Martin Beer, and Timm Harder
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Veterinary medicine ,SF600-1100 - Abstract
Abstract An intravenous pathogenicity index (IVPI) of > 1.2 in chickens or, in case of subtypes H5 and H7, expression of a polybasic hemagglutinin cleavage site (HACS), signals high pathogenicity (HP). Viruses of the H9N2-G1 lineage, which spread across Asia and Africa, are classified to be of low pathogenicity although, in the field, they became associated with severe clinical signs and epizootics in chickens. Here we report on a pre-eminent trait of recent H9N2-G1 isolates from Bangladesh and India, which express a tribasic HACS (motif PAKSKR-GLF; reminiscent of an HPAIV-like polybasic HACS) and compare their features to H9Nx viruses with di- and monobasic HACS from other phylogenetic and geographic origins. In an in vitro assay, the tribasic HACS of H9N2 was processed by furin-like proteases similar to bona fide H5 HPAIV while some dibasic sites showed increased cleavability but monobasic HACS none. Yet, all viruses remained trypsin-dependent in cell culture. In ovo, only tribasic H9N2 viruses were found to replicate in a grossly extended spectrum of embryonic organs. In contrast to all subtype H5/H7 HPAI viruses, tribasic H9N2 viruses did not replicate in endothelial cells either in the chorio-allantoic membrane or in other embryonic tissues. By IVPI, all H9Nx isolates proved to be of low pathogenicity. Pathogenicity assessment of tribasic H9N2-G1 viruses remains problematic. It cannot be excluded that the formation of a third basic amino acid in the HACS forms an intermediate step towards a gain in pathogenicity. Continued observation of the evolution of these viruses in the field is recommended.
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- 2020
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9. Modulation of lethal HPAIV H5N8 clade 2.3.4.4B infection in AIV pre-exposed mallards
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Susanne Koethe, Lorenz Ulrich, Reiner Ulrich, Susanne Amler, Annika Graaf, Timm C. Harder, Christian Grund, Thomas C. Mettenleiter, Franz J. Conraths, Martin Beer, and Anja Globig
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Seropositive ,mallard duck ,HPAIV H5N8 ,clade 2.3.4.4 B ,reservoir host ,AIV pre-exposure ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
ABSTRACTIn 2016/2017, a severe epidemic of HPAIV H5N8 clade 2.3.4.4 group B (H5N8B) affected Europe. To analyse the role of mallards in the spatiotemporal dynamics of global HPAIV H5N8B dispersal, mallards (Anas platyrhynchos), naturally exposed to various AIV and therefore seropositive, were challenged with H5N8B. All experiments were controlled by infection and co-housing of seronegative juvenile Pekin ducklings. All ducks that survived the first infection were re-challenged 21 dpi with the homologous H5N8B strain. After the first H5N8B infection, seropositive mallards showed only mild clinical symptoms. Moderate to low viral shedding, occurring particularly from the oropharynx and lasting for 7 days maximum, led to severe clinical disease of all contact ducklings. All challenged seronegative Pekin ducks and contact ducklings died or had to be euthanized. H5-specific antibodies were detected in surviving birds within 2 weeks. Virus and viral RNA could be isolated from several water samples until 6 and 9 dpi, respectively. Conversely, upon re-infection with homologous H5N8B neither inoculated nor contact ducklings showed any clinical symptoms, nor was an antibody titer increase of seropositive mallards or any seroconversion of contact ducklings observed. Mallard ducks naturally pre-exposed to LPAIV can play a role as a clinically unsuspicious virus reservoir for H5N8B effective in virus transmission. Mallards with homologous immunity did not contribute to virus transmission.
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- 2020
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10. Tetraplex Fluorescent Microbead-Based Immunoassay for the Serodiagnosis of Newcastle Disease Virus and Avian Influenza Viruses in Poultry Sera
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Na Zhao, Christian Grund, Martin Beer, Gang Wang, and Timm C. Harder
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Newcastle disease virus ,avian influenza ,serosurveillance ,fluorescent microspheres ,immunoassay ,multiplex detection ,Medicine - Abstract
Virulent Newcastle disease virus (NDV) as well as highly pathogenic avian influenza (HPAIV) subtypes H5 and H7 induce contagious and lethal systemic disease in poultry. In contrast, low pathogenic AIV H5 and H7 may circulate clinically unnoticed in poultry but eventually generate HPAIV. Low pathogenic NDV strains are widely used as live-attenuated vaccines against ND. Serological tools are essential to conduct active surveillance for infections with notifiable AIV-H5, -H7 and to control vaccination against NDV and HPAIV in poultry populations. Here, recombinant nucleocapsid proteins (NP) of AIV and NDV, and haemagglutinin protein fragment-1 (HA1) of AIV subtypes H5 and H7 were expressed in E. coli. Purification and refolding were required before coating fluorescent microspheres via streptavidin-biotin linkage. The tetraplexed inhibition fluorescent microsphere immunoassay (iFMIA) was then assembled for analysis on a Luminex®-like platform (Bioplex®) using murine monoclonal antibodies specific for each of the four targets. The assay was evaluated by testing galliform poultry sera derived from experimental infections (n = 257) and from farms (n = 250), respectively. The tetraplex iFMIA compared favorably with commercially available ELISAs and the “gold standard” hemagglutination inhibition assay. Tetraplexed iFMIA provided a specific and sensitive tool to detect and discriminate AIV- and NDV-specific antibodies in the sera of galliform poultry.
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- 2022
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11. Connect to Protect: Dynamics and Genetic Connections of Highly Pathogenic Avian Influenza Outbreaks in Poultry from 2016 to 2021 in Germany
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Jacqueline King, Christoph Staubach, Christiane Lüder, Susanne Koethe, Anne Günther, Lina Stacker, Dennis Rubbenstroth, Klaas Dietze, Christian Grund, Franz J. Conraths, Timm Harder, Martin Beer, and Anne Pohlmann
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highly pathogenic avian influenza viruses ,H5N8 ,H5N5 ,clade 2.3.4.4 ,phylogenetic network analyses ,next-generation sequencing ,Microbiology ,QR1-502 - Abstract
During autumn/winter in 2016–2017 and 2020–2021, highly pathogenic avian influenza viruses (HPAIV) caused severe outbreaks in Germany and Europe. Multiple clade 2.3.4.4b H5 HPAI subtypes were responsible for increased mortality in wild birds and high mortality and massive losses in the poultry sector. To clarify putative entry sources and delineate interconnections between outbreaks in poultry holdings and wild birds, we applied whole-genome sequencing and phylodynamic analyses combined with the results of epidemiological outbreak investigations. Varying outbreak dynamics of the distinct reassortants allowed for the identification of individual, putatively wild bird-mediated entries into backyard holdings, several clusters comprising poultry holdings, local virus circulation for several weeks, direct farm-to-farm transmission and potential reassortment within a turkey holding with subsequent spill-over of the novel reassorted virus into the wild bird population. Whole-genome sequencing allowed for a unique high-resolution molecular epidemiology analysis of HPAIV H5Nx outbreaks and is recommended to be used as a standard tool. The presented detailed account of the genetic, temporal, and geographical characteristics of the recent German HPAI H5Nx situation emphasizes the role of poultry holdings as an important source of novel genetic variants and reassortants.
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- 2022
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12. Screening of Healthy Feral Pigeons (Columba livia domestica) in the City of Zurich Reveals Continuous Circulation of Pigeon Paramyxovirus-1 and a Serious Threat of Transmission to Domestic Poultry
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Désirée Annaheim, Barbara Renate Vogler, Brigitte Sigrist, Andrea Vögtlin, Daniela Hüssy, Christian Breitler, Sonja Hartnack, Christian Grund, Jacqueline King, Nina Wolfrum, and Sarah Albini
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Avian Orthoavulavirus-1 ,pigeon paramyxovirus-1 ,feral pigeon ,Columba livia domestica ,reverse transcriptase real-time PCR ,Newcastle disease ,Biology (General) ,QH301-705.5 - Abstract
Pigeon paramyxovirus-1 (PPMV-1) is predominantly isolated from pigeons or doves and forms a separate group of viral strains within Avian Orthoavulavirus-1, the causative agent of Newcastle disease in poultry. Since the introduction of PPMV-1 into Europe in 1981, these strains have rapidly spread all over Europe, and are nowadays considered to be enzootic in feral and hobby pigeons (Columba livia domestica). Infections with PPMV-1 can range from asymptomatic to fatal. To assess whether PPMV-1 continuously circulates in healthy feral pigeons, 396 tissue samples of pigeons from the city of Zurich were tested by reverse transcriptase real-time PCR over the period of one year. PPMV-1-RNA was detected in 41 feral pigeons (10.35%), determined as the dominant European genotype VI.2.1.1.2.2. In 38 of the 41 pigeons where organ samples tested positive, PPMV-1-RNA was also detected in either choana or cloaca swabs. There were no significant differences in positivity rates between seasons, age, and sex. The current study shows that feral pigeons without clinical signs of disease can harbour and most likely excrete PPMV-1. Spill-over into free-range holdings of chickens are therefore possible, as observed in a recent outbreak of Newcastle disease in laying hens due to PPMV-1 genotype VI.2.1.1.2.2. in the canton of Zurich in January 2022.
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- 2022
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13. Genetic Characterization and Zoonotic Potential of Highly Pathogenic Avian Influenza Virus A(H5N6/H5N5), Germany, 2017–2018
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Anne Pohlmann, Donata Hoffmann, Christian Grund, Susanne Koethe, Daniela Hüssy, Simone M. Meier, Jacqueline King, Jan Schinköthe, Reiner Ulrich, Timm Harder, and Martin Beer
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highly pathogenic avian influenza ,HPAI ,H5N6 ,H5N5 ,H5N8 ,zoonotic potential ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
We genetically characterized highly pathogenic avian influenza virus A(H5N6) clade 2.3.4.4b isolates found in Germany in 2017–2018 and assessed pathogenicity of representative H5N5 and H5N6 viruses in ferrets. These viruses had low pathogenicity; however, continued characterization of related isolates is warranted because of their high potential for reassortment.
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- 2019
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14. Neuraminidase-associated plasminogen recruitment enables systemic spread of natural avian Influenza viruses H3N1.
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Jacob Schön, Angele Breithaupt, Dirk Höper, Jacqueline King, Anne Pohlmann, Rokshana Parvin, Klaus-Peter Behr, Bernd-Andreas Schwarz, Martin Beer, Jürgen Stech, Timm Harder, and Christian Grund
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Repeated outbreaks due to H3N1 low pathogenicity avian influenza viruses (LPAIV) in Belgium were associated with unusually high mortality in chicken in 2019. Those events caused considerable economic losses and prompted restriction measures normally implemented for eradicating high pathogenicity avian influenza viruses (HPAIV). Initial pathology investigations and infection studies suggested this virus to be able to replicate systemically, being very atypical for H3 LPAIV. Here, we investigate the pathogenesis of this H3N1 virus and propose a mechanism explaining its unusual systemic replication capability. By intravenous and intracerebral inoculation in chicken, we demonstrate systemic spread of this virus, extending to the central nervous system. Endoproteolytic viral hemagglutinin (HA) protein activation by either tissue-restricted serine peptidases or ubiquitous subtilisin-like proteases is the functional hallmark distinguishing (H5 or H7) LPAIV from HPAIV. However, luciferase reporter assays show that HA cleavage in case of the H3N1 strain in contrast to the HPAIV is not processed by intracellular proteases. Yet the H3N1 virus replicates efficiently in cell culture without trypsin, unlike LPAIVs. Moreover, this trypsin-independent virus replication is inhibited by 6-aminohexanoic acid, a plasmin inhibitor. Correspondingly, in silico analysis indicates that plasminogen is recruitable by the viral neuraminidase for proteolytic activation due to the loss of a strongly conserved N-glycosylation site at position 130. This mutation was shown responsible for plasminogen recruitment and neurovirulence of the mouse brain-passaged laboratory strain A/WSN/33 (H1N1). In conclusion, our findings provide good evidence in natural chicken strains for N1 neuraminidase-operated recruitment of plasminogen, enabling systemic replication leading to an unusual high pathogenicity phenotype. Such a gain of function in naturally occurring AIVs representing an established human influenza HA-subtype raises concerns over potential zoonotic threats.
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- 2021
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15. Det fundne og det tabte: To nationer under Gud
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Christian Grund Sørensen
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Kaj Munk, Genforeningen, Sønderjylland, Tyskland, nation ,History of scholarship and learning. The humanities ,AZ20-999 - Abstract
The found and the Lost: Two Nations under God. Kaj Munk and the question of Southern Jutland. The aim of this article is to present and discuss the view of Danish pastor, playwright, author, and resistance martyr Kaj Munk (1898-1944) regarding the reunion of Denmark and Southern Jutland in 1920. In Munk’s view Southern Jutland and the border to Germany is of central importance to the Danish national identity. The population remained culturally Danish under German rule. However, the reunion and the close relationship with Germany was challenged during the rise of the Third Reich, and eventually the occupation of Denmark. Kaj Munk’s nuanced reflections on the cohabitation of neighbouring countries reject demonization and nationalistic superiority thinking. In Munk’s understanding “fronts” and “bridges” are necessary in international cooperation. The front to protect intrinsic values and avoid appropriation, the bridges to bridge divides between the two nations under God. Munk is an example of a peaceful, acknowledging approach to international cohabitation, though with a strong sense of cultural consistency.
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- 2020
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16. SARS-CoV-2 in fruit bats, ferrets, pigs, and chickens: an experimental transmission study
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Kore Schlottau, PhD, Melanie Rissmann, DVM, Annika Graaf, DVM, Jacob Schön, PhD, Julia Sehl, DVM, Claudia Wylezich, PhD, Dirk Höper, PhD, Thomas C Mettenleiter, ProfPhD, Anne Balkema-Buschmann, DVM, Timm Harder, ProfDVM, Christian Grund, DVM, Donata Hoffmann, DVM, Angele Breithaupt, DVM, and Martin Beer, ProfDVM
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Medicine (General) ,R5-920 ,Microbiology ,QR1-502 - Abstract
Summary: Background: In December, 2019, a novel zoonotic severe acute respiratory syndrome-related coronavirus emerged in China. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became pandemic within weeks and the number of human infections and severe cases is increasing. We aimed to investigate the susceptibilty of potential animal hosts and the risk of anthropozoonotic spill-over infections. Methods: We intranasally inoculated nine fruit bats (Rousettus aegyptiacus), ferrets (Mustela putorius), pigs (Sus scrofa domesticus), and 17 chickens (Gallus gallus domesticus) with 105 TCID50 of a SARS-CoV-2 isolate per animal. Direct contact animals (n=3) were included 24 h after inoculation to test viral transmission. Animals were monitored for clinical signs and for virus shedding by nucleic acid extraction from nasal washes and rectal swabs (ferrets), oral swabs and pooled faeces samples (fruit bats), nasal and rectal swabs (pigs), or oropharyngeal and cloacal swabs (chickens) on days 2, 4, 8, 12, 16, and 21 after infection by quantitative RT-PCR (RT-qPCR). On days 4, 8, and 12, two inoculated animals (or three in the case of chickens) of each species were euthanised, and all remaining animals, including the contacts, were euthanised at day 21. All animals were subjected to autopsy and various tissues were collected for virus detection by RT-qPCR, histopathology immunohistochemistry, and in situ hybridisation. Presence of SARS-CoV-2 reactive antibodies was tested by indirect immunofluorescence assay and virus neutralisation test in samples collected before inoculation and at autopsy. Findings: Pigs and chickens were not susceptible to SARS-CoV-2. All swabs, organ samples, and contact animals were negative for viral RNA, and none of the pigs or chickens seroconverted. Seven (78%) of nine fruit bats had a transient infection, with virus detectable by RT-qPCR, immunohistochemistry, and in situ hybridisation in the nasal cavity, associated with rhinitis. Viral RNA was also identified in the trachea, lung, and lung-associated lymphatic tissue in two animals euthanised at day 4. One of three contact bats became infected. More efficient virus replication but no clinical signs were observed in ferrets, with transmission to all three direct contact animals. Mild rhinitis was associated with viral antigen detection in the respiratory and olfactory epithelium. Prominent viral RNA loads of 0–104 viral genome copies per mL were detected in the upper respiratory tract of fruit bats and ferrets, and both species developed SARS-CoV-2-reactive antibodies reaching neutralising titres of up to 1/1024 after 21 days. Interpretation: Pigs and chickens could not be infected intranasally by SARS-CoV-2, whereas fruit bats showed characteristics of a reservoir host. Virus replication in ferrets resembled a subclinical human infection with efficient spread. Ferrets might serve as a useful model for further studies—eg, testing vaccines or antivirals. Funding: German Federal Ministry of Food and Agriculture.
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- 2020
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17. Engineered recombinant protein products of the avian paramyxovirus type-1 nucleocapsid and phosphoprotein genes for serological diagnosis
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Na Zhao, Christian Grund, Martin Beer, and Timm C. Harder
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Newcastle disease virus ,Recombinant protein ,Subtype-specific serology ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Virulent Newcastle disease virus (NDV, avian Avulavirus-1, APMV-1) induces a highly contagious and lethal systemic disease in gallinaceous poultry. APMV-1 antibody detection is used for surveillance and to control vaccination, but is hampered by cross-reactivity to other subtypes of avian Avulaviruses. Data are lacking concerning the applicability of NDV V proteins as differential diagnostic marker to distinguish vaccinated from virus-infected birds (DIVA strategy). Methods Full length and C-terminally truncated nucleocapsid (NP) protein, and the unique C-terminal regions of the phospho- (P) and V proteins of the NDV LaSota strain were bacterially expressed as fusion proteins with the multimerization domain of the human C4 binding protein, and used as diagnostic antigens in indirect ELISA. Results When used as diagnostic antigen in indirect ELISAs, recombinant full-length proved to be a sensitive target to detect seroconversion in chickens after APMV-1 vaccination and infection, but revealed some degree of cross reactivity with sera raised against other APMV subtypes. Cross reactivity was abolished but also sensitivity decreased when employing a C-terminal fragment of the NP of NDV as diagnostic antigen. Antibodies to the NDV V protein were mounted in poultry following NDV infection but also, albeit at lower rates and titers, after vaccination with attenuated NDV vaccines. V-specific seroconversion within the flock was incomplete and titers in individual bird transient. Conclusions Indirect ELISA based on bacterially expressed recombinant full-length NP compared favorably with a commercial NDV ELISA based on whole virus antigen, but cross reactivity between the NP proteins of different APMV subtypes could compromise specificity. However, specificity increased when using a less conserved C-terminal fragment of NP instead. Moreover, a serological DIVA strategy built on the NDV V protein was not feasible due to reduced immunogenicity of the V protein and frequent use of live-attenuated NDV vaccines.
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- 2018
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18. A Semiquantitative Scoring System for Histopathological and Immunohistochemical Assessment of Lesions and Tissue Tropism in Avian Influenza
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Maria Landmann, David Scheibner, Annika Graaf, Marcel Gischke, Susanne Koethe, Olanrewaju I. Fatola, Barbara Raddatz, Thomas C. Mettenleiter, Martin Beer, Christian Grund, Timm Harder, Elsayed M. Abdelwhab, and Reiner Ulrich
- Subjects
avian influenza virus ,poultry ,histopathology ,immunohistochemistry ,semiquantitative scoring system ,Microbiology ,QR1-502 - Abstract
The main findings of the post-mortem examination of poultry infected with highly pathogenic avian influenza viruses (HPAIV) include necrotizing inflammation and viral antigen in multiple organs. The lesion profile displays marked variability, depending on viral subtype, strain, and host species. Therefore, in this study, a semiquantitative scoring system was developed to compare histopathological findings across a wide range of study conditions. Briefly, the severity of necrotizing lesions in brain, heart, lung, liver, kidney, pancreas, and/or lymphocytic depletion in the spleen is scored on an ordinal four-step scale (0 = unchanged, 1 = mild, 2 = moderate, 3 = severe), and the distribution of the viral antigen in parenchymal and endothelial cells is evaluated on a four-step scale (0 = none, 1 = focal, 2 = multifocal, 3 = diffuse). These scores are used for a meta-analysis of experimental infections with H7N7 and H5N8 (clade 2.3.4.4b) HPAIV in chickens, turkeys, and ducks. The meta-analysis highlights the rather unique endotheliotropism of these HPAIV in chickens and a more severe necrotizing encephalitis in H7N7-HPAIV-infected turkeys. In conclusion, the proposed scoring system can be used to condensate HPAIV-typical pathohistological findings into semiquantitative data, thus enabling systematic phenotyping of virus strains and their tissue tropism.
- Published
- 2021
- Full Text
- View/download PDF
19. Outbreaks among Wild Birds and Domestic Poultry Caused by Reassorted Influenza A(H5N8) Clade 2.3.4.4 Viruses, Germany, 2016
- Author
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Anne Pohlmann, Elke Starick, Timm Harder, Christian Grund, Dirk Höper, Anja Globig, Christoph Staubach, Klaas Dietze, Günter Strebelow, Reiner G. Ulrich, Jan Schinköthe, Jens P. Teifke, Franz J. Conraths, Thomas C. Mettenleiter, and Martin Beer
- Subjects
avian influenza virus ,highly pathogenic avian influenza viruses ,HPAIV ,H5N8 ,reassortant ,viruses ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
In November 2016, an influenza A(H5N8) outbreak caused deaths of wild birds and domestic poultry in Germany. Clade 2.3.4.4 virus was closely related to viruses detected at the Russia–Mongolia border in 2016 but had new polymerase acidic and nucleoprotein segments. These new strains may be more efficiently transmitted to and shed by birds.
- Published
- 2017
- Full Text
- View/download PDF
20. Vaccine Quality Is a Key Factor to Determine Thermal Stability of Commercial Newcastle Disease (ND)Vaccines
- Author
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Nabila Osman, Danny Goovaerts, Serageldeen Sultan, Jeremy Salt, and Christian Grund
- Subjects
heat stability ,Newcastle disease virus ,paramyxovirus ,vaccine quality ,vaccine stability ,Medicine - Abstract
Vaccination against Newcastle disease (ND), a devastating viral disease of chickens, is often hampered by thermal inactivation of the live vaccines, in particular in tropical and hot climate conditions. In the past, “thermostable” vaccine strains (I-2) were proposed to overcome this problem but previous comparative studies did not include formulation-specific factors of commercial vaccines. In the current study, we aimed to verify the superior thermal stability of commercially formulated I-2 strains by comparing six commercially available ND vaccines. Subjected to 37 °C as lyophilized preparations, two vaccines containing I-2 strains were more sensitive to inactivation than a third I-2 vaccine or compared to three other vaccines based on different ND strains. However, reconstitution strains proved to have a comparable tenacity. Interestingly, all vaccines still retained a sufficient virus dose for protection (106 EID50) after 1 day at 37 °C. These results suggest that there are specific factors that influence thermal stability beyond the strain-specific characteristics. Exposing ND vaccines to elevated temperatures of 51 and 61 °C demonstrated that inactivation of all dissolved vaccines including I-2 vaccine strains occurred within 2 to 4 h. The results revealed important differences among the vaccines and emphasize the importance of the quality of a certain vaccine preparation rather than the strain it contains. These data highlight that regardless of the ND strain used for vaccine preparation, the appropriate cold chain is mandatory for keeping live ND vaccines efficiency in hot climates.
- Published
- 2021
- Full Text
- View/download PDF
21. Decisions on Extending Group Membership—Evidence from a Public Good Experiment
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Christian Grund, Christine Harbring, Kirsten Thommes, and Katja Rebecca Tilkes
- Subjects
cooperation ,public good game ,group membership ,experiment ,Technology ,Social Sciences - Abstract
We experimentally compare the consequences for group cooperation of two decision mechanisms involving the extension of group membership. We analyze an exogenous decision (random draw) and an endogenous decision (made by a particular group member) mechanism to extend a temporary agent’s group membership. Our results reveal that the prospect of group membership extension affects not only the temporary but also the permanent group members’ contributions with an endogenous mechanism.
- Published
- 2020
- Full Text
- View/download PDF
22. Protection of Chickens with Maternal Avian Influenza Virus (AIV) Immunity after Vaccination with a Recombinant AIV-Newcastle Disease Vector
- Author
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Magdalena Murr, Olayinka Asala, Axel Karger, Christian Grund, Thomas C. Mettenleiter, and Angela Römer-Oberdörfer
- Subjects
avian influenza, H5N1, Newcastle disease, vector vaccine, DIVA, maternal immunity ,General Works - Abstract
Highly pathogenic avian influenza virus (HPAIV) belongs to the Orthomyxoviridae family and causes a systemic and highly lethal disease in poultry. Vaccination with recombinant Newcastle disease vector viruses (NDV) expressing the hemagglutinin (HA) of HPAIV H5N1 induces high antibody titers in chickens free of specific pathogens, conveying protection against a lethal infection with HPAIV H5N1. Protection of chickens possessing maternally derived NDV immunity was achieved after the replacement of the surface proteins of NDV, the fusion protein (F), and the hemagglutinin-neuraminidase protein (HN) against those of avian paramyxovirus serotype 8. However, maternal AIV antibodies (αAIV-MDA+) still interfere with vaccine virus replication, resulting in inefficient protection. For our study, recombinant rNDVsolH5_H5 was generated. The insertion of a transgene encoding a truncated soluble HA between the NDV phosphoprotein and matrix protein genes—in addition to the gene encoding a membrane-bound HA inserted between the NDV, F and HN of the lentogenic NDV Clone 30 —was expected to increase the total amount of HA expressed by the recombinant virus. Western blot and mass spectrometry analyses confirmed the increase in HA expression compared to the parental rNDVH5 expressing only the full-length HA. The protective efficacy of the newly generated recombinant NDV was tested in an animal experiment. αAIV-MDA+ chickens were vaccinated either 7, 14, or 21 days after hatching. A homologous challenge infection was carried out three weeks later. Although the youngest chickens showed the highest titer of αAIV-MDA, there were no AIV antibodies detectable 21 days after vaccination. However, 40% of vaccinated chickens were protected, while 85% and 100% protection was observed in the middle-aged and oldest chickens, which had low and no detectable levels of αAIV-MDA, and moderate and high AIV antibody levels after vaccination, respectively. Challenge infection of non-vaccinated chickens resulted in high mortality.
- Published
- 2020
- Full Text
- View/download PDF
23. A Novel Recombinant Newcastle Disease Virus Vectored DIVA Vaccine against Peste des Petits Ruminants in Goats
- Author
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Magdalena Murr, Bernd Hoffmann, Christian Grund, Angela Römer-Oberdörfer, and Thomas C. Mettenleiter
- Subjects
Newcastle disease virus ,peste des petits ruminants ,small ruminant morbillivirus ,vector vaccine ,DIVA ,mammals ,Medicine - Abstract
Peste des petits ruminants virus (PPRV, species: small ruminant morbillivirus) is the causative agent of the eponymous notifiable disease, the peste des petits ruminants (PPR) in wild and domestic sheep and goats. Mortality rates vary between 50% and 100%, causing significant losses of estimated 1.5 to 2 billion US Dollars per year. Live-attenuated PPRV vaccine strains are used in the field for disease prevention, but the application of a more thermostable vaccine enabling differentiation between infected and vaccinated animals (DIVA) would be highly desirable to achieve the goal of global disease eradication. We generated a recombinant Newcastle disease virus (rNDV) based on the live-attenuated NDV Clone 30 that expresses the surface protein hemagglutinin (H) of PPRV strain Kurdistan/11 (rNDV_HKur). In vitro analyses confirmed transgene expression as well as virus replication in avian, caprine, and ovine cells. Two consecutive subcutaneous vaccinations of German domestic goats with rNDV_HKur prevented clinical signs and hematogenic dissemination after an intranasal challenge with virulent PPRV Kurdistan/11. Virus shedding by different routes was reduced to a similar extent as after vaccination with the live-attenuated PPRV strain Nigeria 75/1. Goats that were either not vaccinated or inoculated with parental rNDV were used as controls. In summary, we demonstrate in a proof-of-concept study that an NDV vectored vaccine can protect against PPR. Furthermore, it provides DIVA-applicability and a high thermal tolerance.
- Published
- 2020
- Full Text
- View/download PDF
24. Highly Pathogenic Avian Influenza H5N8 Clade 2.3.4.4b in Germany in 2016/2017
- Author
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Anja Globig, Christoph Staubach, Carola Sauter-Louis, Klaas Dietze, Timo Homeier-Bachmann, Carolina Probst, Jörn Gethmann, Klaus R. Depner, Christian Grund, Timm C. Harder, Elke Starick, Anne Pohlmann, Dirk Höper, Martin Beer, Thomas C. Mettenleiter, and Franz J. Conraths
- Subjects
highly pathogenic avian influenza ,H5N8 ,clade 2.3.4.4b ,Germany ,wild water birds ,outbreak investigations ,Veterinary medicine ,SF600-1100 - Abstract
Here, we report on the occurrence of highly pathogenic avian influenza (HPAI) H5Nx clade 2.3.4.4b in Germany. Between November 8, 2016, and September 30, 2017, more than 1,150 cases of HPAI H5Nx clade 2.3.4.4b in wild birds and 107 outbreaks in birds kept in captivity (92 poultry holdings and 15 zoos/animal parks) were reported in Germany. This HPAI epidemic is the most severe recorded in Germany so far. The viruses were apparently introduced by migratory birds, sparking an epidemic among wild birds across Germany with occasional incursions into poultry holdings, zoos and animal parks, which were usually rapidly detected and controlled by stamping out. HPAI viruses (mainly subtype H5N8, in a few cases also H5N5) were found in dead wild birds of at least 53 species. The affected wild birds were water birds (including gulls, storks, herons, and cormorants) and scavenging birds (birds of prey, owls, and crows). In a number of cases, substantial gaps in farm biosecurity may have eased virus entry into the holdings. In a second wave of the epidemic starting from February 2017, there was epidemiological and molecular evidence for virus transmission of the infections between commercial turkey holdings in an area of high poultry density, which caused approximately 25% of the total number of outbreaks in poultry. Biosecurity measures in poultry holdings should be adapted. This includes, inter alia, wearing of stable-specific protective clothing and footwear, cleaning, and disinfection of equipment that has been in contact with birds and prevention of contacts between poultry and wild water birds.
- Published
- 2018
- Full Text
- View/download PDF
25. Influenza A(H5N8) Virus Similar to Strain in Korea Causing Highly Pathogenic Avian Influenza in Germany
- Author
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Timm Harder, Sebastian Maurer-Stroh, Anne Pohlmann, Elke Starick, Detlef Höreth-Böntgen, Karin Albrecht, Gunter Pannwitz, Jens P. Teifke, Vithiagaran Gunalan, Raphael T.C. Lee, Carola Sauter-Louis, Timo Homeier, Christoph Staubach, Carola Wolf, Günter Strebelow, Dirk Höper, Christian Grund, Franz J. Conraths, Thomas C. Mettenleiter, and Martin Beer
- Subjects
influenza A virus ,H5N8 subtype ,highly pathogenic ,poultry ,wild birds ,zoonoses ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Highly pathogenic avian influenza (H5N8) virus, like the recently described H5N8 strain from Korea, was detected in November 2014 in farmed turkeys and in a healthy common teal (Anas crecca) in northeastern Germany. Infected wild birds possibly introduced this virus.
- Published
- 2015
- Full Text
- View/download PDF
26. Highly Pathogenic Avian Influenza Virus (H5N1) in Frozen Duck Carcasses, Germany, 2007
- Author
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Timm C. Harder, Jürgen Teuffert, Elke Starick, Jörn Gethmann, Christian Grund, Sasan Fereidouni, Markus Durban, Karl-Heinz Bogner, Antonie Neubauer-Juric, Reinhard Repper, Andreas Hlinak, Andreas Engelhardt, Axel Nöckler, Krzysztof Smietanka, Zenon Minta, Matthias Kramer, Anja Globig, Thomas C. Mettenleiter, Franz J. Conraths, and Martin Beer
- Subjects
Highly pathogenic avian influenza ,food safety ,H5N1 ,epidemiology ,phylogeny ,research ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
We conducted phylogenetic and epidemiologic analyses to determine sources of outbreaks of highly pathogenic avian influenza virus (HPAIV), subtype H5N1, in poultry holdings in 2007 in Germany, and a suspected incursion of HPAIV into the food chain through contaminated deep-frozen duck carcasses. In summer 2007, HPAIV (H5N1) outbreaks in 3 poultry holdings in Germany were temporally, spatially, and phylogenetically linked to outbreaks in wild aquatic birds. Detection of HPAIV (H5N1) in frozen duck carcass samples of retained slaughter batches of 1 farm indicated that silent infection had occurred for some time before the incidental detection. Phylogenetic analysis established a direct epidemiologic link between HPAIV isolated from duck meat and strains isolated from 3 further outbreaks in December 2007 in backyard chickens that had access to uncooked offal from commercial deep-frozen duck carcasses. Measures that will prevent such undetected introduction of HPAIV (H5N1) into the food chain are urgently required.
- Published
- 2009
- Full Text
- View/download PDF
27. Protection and Virus Shedding of Falcons Vaccinated against Highly Pathogenic Avian Influenza A Virus (H5N1)
- Author
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Michael Lierz, Hafez M. Hafez, Robert Klopfleisch, Dörte Lüschow, Christine Prusas, Jens P. Teifke, Miriam Rudolf, Christian Grund, Donata Kalthoff, Thomas C. Mettenleiter, Martin Beer, and Timm Harder
- Subjects
Birds of prey ,falcon hybrids ,highly pathogenic avian influenza ,challenge ,antibody titer ,histopathology ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Because fatal infections with highly pathogenic avian influenza A (HPAI) virus subtype H5N1 have been reported in birds of prey, we sought to determine detailed information about the birds’ susceptibility and protection after vaccination. Ten falcons vaccinated with an inactivated influenza virus (H5N2) vaccine seroconverted. We then challenged 5 vaccinated and 5 nonvaccinated falcons with HPAI (H5N1). All vaccinated birds survived; all unvaccinated birds died within 5 days. For the nonvaccinated birds, histopathologic examination showed tissue degeneration and necrosis, immunohistochemical techniques showed influenza virus antigen in affected tissues, and these birds shed high levels of infectious virus from the oropharynx and cloaca. Vaccinated birds showed no influenza virus antigen in tissues and shed virus at lower titers from the oropharynx only. Vaccination could protect these valuable birds and, through reduced virus shedding, reduce risk for transmission to other avian species and humans.
- Published
- 2007
- Full Text
- View/download PDF
28. Different regions of the newcastle disease virus fusion protein modulate pathogenicity.
- Author
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Sandra Heiden, Christian Grund, Anja Röder, Harald Granzow, Denis Kühnel, Thomas C Mettenleiter, and Angela Römer-Oberdörfer
- Subjects
Medicine ,Science - Abstract
Newcastle disease virus (NDV), also designated as Avian paramyxovirus type 1 (APMV-1), is the causative agent of a notifiable disease of poultry but it exhibits different pathogenicity dependent on the virus strain. The molecular basis for this variability is not fully understood. The efficiency of activation of the fusion protein (F) is determined by presence or absence of a polybasic amino acid sequence at an internal proteolytic cleavage site which is a major determinant of NDV virulence. However, other determinants of pathogenicity must exist since APMV-1 of high (velogenic), intermediate (mesogenic) and low (lentogenic) virulence specify a polybasic F cleavage site. We aimed at elucidation of additional virulence determinants by constructing a recombinant virus that consists of a lentogenic NDV Clone 30 backbone and the F protein gene from a mesogenic pigeon paramyxovirus-1 (PPMV-1) isolate with an intracerebral pathogenicity index (ICPI) of 1.1 specifying the polybasic sequence R-R-K-K-R*F motif at the cleavage site. The resulting virus was characterized by an ICPI of 0.6, indicating a lentogenic pathotype. In contrast, alteration of the cleavage site G-R-Q-G-R*L of the lentogenic Clone 30 to R-R-K-K-R*F resulted in a recombinant virus with an ICPI of 1.36 which was higher than that of parental PPMV-1. Substitution of different regions of the F protein of Clone 30 by those of PPMV-1, while maintaining the polybasic amino acid sequence at the F cleavage site, resulted in recombinant viruses with ICPIs ranging from 0.59 to 1.36 suggesting that virulence is modulated by regions of the F protein other than the polybasic cleavage site.
- Published
- 2014
- Full Text
- View/download PDF
29. Limited Susceptibility of Chickens, Turkeys, and Mice to Pandemic (H1N1) 2009 Virus
- Author
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Donata Kalthoff, Christian Grund, Timm C. Harder, Elke Lange, Thomas W. Vahlenkamp, Thomas C. Mettenleiter, and Martin Beer
- Subjects
Swine influenza ,pandemic (H1N1) 2009 ,pathogenicity ,transmission ,chickens ,turkeys ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
To determine susceptibility of chickens, turkeys, and mice to pandemic (H1N1) 2009 virus, we conducted contact exposure and inoculation experiments. We demonstrated that chickens were refractory to infection. However, oculo-oronasally inoculated turkeys and intranasally inoculated mice seroconverted without clinical signs of infection.
- Published
- 2010
- Full Text
- View/download PDF
30. Chimeric newcastle disease virus protects chickens against avian influenza in the presence of maternally derived NDV immunity.
- Author
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Constanze Steglich, Christian Grund, Kristina Ramp, Angele Breithaupt, Dirk Höper, Günther Keil, Jutta Veits, Mario Ziller, Harald Granzow, Thomas C Mettenleiter, and Angela Römer-Oberdörfer
- Subjects
Medicine ,Science - Abstract
Newcastle disease virus (NDV), an avian paramyxovirus type 1, is a promising vector for expression of heterologous proteins from a variety of unrelated viruses including highly pathogenic avian influenza virus (HPAIV). However, pre-existing NDV antibodies may impair vector virus replication, resulting in an inefficient immune response against the foreign antigen. A chimeric NDV-based vector with functional surface glycoproteins unrelated to NDV could overcome this problem. Therefore, an NDV vector was constructed which carries the fusion (F) and hemagglutinin-neuraminidase (HN) proteins of avian paramyxovirus type 8 (APMV-8) instead of the corresponding NDV proteins in an NDV backbone derived from the lentogenic NDV Clone 30 and a gene expressing HPAIV H5 inserted between the F and HN genes. After successful virus rescue by reverse genetics, the resulting chNDVFHN PMV8H5 was characterized in vitro and in vivo. Expression and virion incorporation of the heterologous proteins was verified by Western blot and electron microscopy. Replication of the newly generated recombinant virus was comparable to parental NDV in embryonated chicken eggs. Immunization with chNDVFHN PMV8H5 stimulated full protection against lethal HPAIV infection in chickens without as well as with maternally derived NDV antibodies. Thus, tailored NDV vector vaccines can be provided for use in the presence or absence of routine NDV vaccination.
- Published
- 2013
- Full Text
- View/download PDF
31. Highly pathogenic avian influenza virus infection of mallards with homo- and heterosubtypic immunity induced by low pathogenic avian influenza viruses.
- Author
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Sasan R Fereidouni, Elke Starick, Martin Beer, Hendrik Wilking, Donata Kalthoff, Christian Grund, Rafaela Häuslaigner, Angele Breithaupt, Elke Lange, and Timm C Harder
- Subjects
Medicine ,Science - Abstract
The potential role of wild birds as carriers of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 is still a matter of debate. Consecutive or simultaneous infections with different subtypes of influenza viruses of low pathogenicity (LPAIV) are very common in wild duck populations. To better understand the epidemiology and pathogenesis of HPAIV H5N1 infections in natural ecosystems, we investigated the influence of prior infection of mallards with homo- (H5N2) and heterosubtypic (H4N6) LPAIV on exposure to HPAIV H5N1. In mallards with homosubtypic immunity induced by LPAIV infection, clinical disease was absent and shedding of HPAIV from respiratory and intestinal tracts was grossly reduced compared to the heterosubtypic and control groups (mean GEC/100 microl at 3 dpi: 3.0 x 10(2) vs. 2.3 x 10(4) vs. 8.7 x 10(4); p
- Published
- 2009
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- View/download PDF
32. ElliPose: Stereoscopic 3D Human Pose Estimation by Fitting Ellipsoids.
- Author
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Christian Grund, Julian Tanke, and Juergen Gall
- Published
- 2023
- Full Text
- View/download PDF
33. What Object Should I Use? - Task Driven Object Detection.
- Author
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Johann Sawatzky, Yaser Souri, Christian Grund, and Jürgen Gall
- Published
- 2019
- Full Text
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34. Competing trade mechanisms and monotone mechanism choice.
- Author
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Eberhard Feess, Christian Grund, Markus Walzl, and Ansgar Wohlschlegel
- Published
- 2020
- Full Text
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35. Working-time mismatch and job satisfaction of junior academics
- Author
-
Irina Frei and Christian Grund
- Subjects
Economics and Econometrics ,Business and International Management - Abstract
We examine the role of working-time mismatches (defined as the difference between actual and desired weekly working hours) in academics’ job satisfaction. In doing so, we investigate how academics’ career stage (predoc vs. postdoc) and contract status (part-time vs. full-time employment) moderate the relation between a mismatch in working hours and job-related well-being. Our results are based on longitudinal survey data among junior academics in the STEM fields indicate that mismatches in working hours are prevalent in academia and are associated with a loss of job satisfaction. In this context, overemployment (working more than desired) tends to unfold more severe consequences with respect to job satisfaction compared to underemployment. We find evidence for a similar reaction of doctoral students and postdocs with respect to job satisfaction when experiencing a working-time mismatch. Part-time employment positively moderates the link between working-time mismatch and job satisfaction for the case of underemployment.
- Published
- 2022
36. Job Placement via Private vs. Public Employment Agencies: Investigating Selection Effects and Job Match Quality in Germany
- Author
-
Adam Ayaita, Christian Grund, and Lisa Pütz
- Subjects
Management of Technology and Innovation ,General Economics, Econometrics and Finance ,General Business, Management and Accounting - Abstract
Schmalenbachs Zeitschrift f��r betriebswirtschaftliche Forschung 74(January), 26 (2022). doi:10.1007/s41471-021-00129-1, Published by Westdt. Verl., K��ln ; Opladen
- Published
- 2022
37. Works Councils as Gatekeepers: Codetermination, Monitoring Practices, and Job Satisfaction
- Author
-
Christian Grund, Dirk Sliwka, and Krystina Titz
- Subjects
History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2023
38. Monetary Rewards, Hierarchy Level and Working Hours as Drivers of Employees' Self-Evaluations
- Author
-
Christian Grund and Alexandra Soboll
- Subjects
History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2023
39. Peers at work: Economic real-effort experiments in the presence of virtual co-workers.
- Author
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Andrea Bönsch, Jonathan Wendt, Heiko Overath, özgür Gürerk, Christine Harbring, Christian Grund, Thomas Kittsteiner, and Torsten W. Kuhlen
- Published
- 2017
- Full Text
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40. Passive A-Band Wind Sounder (PAWS) for Measuring Tropospheric Wind Velocity.
- Author
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Robert Pierce, Shane Roark, Christian Grund, Philip Slaymaker, Pei Huang 0007, and Paul Kaptchen
- Published
- 2008
- Full Text
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41. The Role of Employees’ Age for the Relation Between Job Autonomy and Sickness Absence
- Author
-
Maike Rubin and Christian Grund
- Subjects
Negotiating ,media_common.quotation_subject ,Control (management) ,Public Health, Environmental and Occupational Health ,Work content ,Affect (psychology) ,Mental health ,Job Satisfaction ,language.human_language ,German ,Mental Health ,Work (electrical) ,Surveys and Questionnaires ,language ,Humans ,Job satisfaction ,Psychology ,Social psychology ,Autonomy ,media_common - Abstract
OBJECTIVE We investigate whether job autonomy is associated with employees' sickness absence. In particular, we examine the role of employees' age for this relationship. METHODS We can make use of the representative German Study of Mental Health at Work data (n = 3099 employees) and control for relevant covariates. RESULTS Applying theoretical consideration such as the Job Demand Control Model, we do find evidence for an inverse relation between employees' job autonomy and days of sickness absence. This relation is only weakly mediated by job satisfaction and particularly relevant for more senior employees. CONCLUSIONS Theoretical implications are aimed at extending the existing theoretical models by individuals age and derive age-specific propositions. Managerial implications include recommendations which directly affect the individuals work content with regard to the use of our definition of job autonomy.
- Published
- 2021
42. Content, Context & Connectivity Persuasive Interplay.
- Author
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Christian Grund Sørensen
- Published
- 2013
- Full Text
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43. Emergence and spread of novel H5N8, H5N5 and H5N1 clade 2.3.4.4 highly pathogenic avian influenza in 2020
- Author
-
Thamer Al Kafagi, Jacqueline King, Azimkhan Tegzhanov, Timm C. Harder, Martin Beer, Anne Pohlmann, Sultanov Akhmetzhan, Ian H. Brown, Adam Brouwer, Talgat Karibayev, Scott M. Reid, Nikolay Zinyakov, Ashley C. Banyard, Ilya Chvala, Saduakassova Meruyert, Nicola S. Lewis, Steve Essen, Christian Grund, Ron A. M. Fouchier, Alexander M. P. Byrne, Victor Irza, Elliot Whittard, and Virology
- Subjects
0301 basic medicine ,Letter ,Epidemiology ,animal diseases ,Highly pathogenic ,030106 microbiology ,Immunology ,Zoology ,HPAI ,Biology ,medicine.disease_cause ,Microbiology ,Poultry ,Disease Outbreaks ,Russia ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Virology ,Drug Discovery ,medicine ,emergence ,Animals ,Influenza A Virus, H5N8 Subtype ,SDG 2 - Zero Hunger ,Clade ,Phylogeny ,Netherlands ,Food security ,Influenza A Virus, H5N1 Subtype ,Whole Genome Sequencing ,avian ,virus diseases ,Outbreak ,General Medicine ,Influenza ,Kazakhstan ,Influenza A virus subtype H5N1 ,030104 developmental biology ,Infectious Diseases ,Migratory waterfowl ,Influenza A virus ,Influenza in Birds ,Iraq ,Eurasia ,Veterinary public health ,Parasitology ,Russian federation - Abstract
Analyses of HPAI H5 viruses from poultry outbreaks across a wide Eurasian region since July 2020 including the Russian Federation, Republics of Iraq and Kazakhstan, and recent detections in migratory waterfowl in the Netherlands, revealed undetected maintenance of H5N8, likely in galliform poultry since 2017/18 and both H5N5 and H5N1. All viruses belong to A/H5 clade 2.3.4.4b with closely related HA genes. Heterogeneity in Eurasian H5Nx HPAI emerging variants threatens poultry production, food security and veterinary public health.
- Published
- 2021
44. Genuine lethal infection of a wood pigeon (Columba palumbus) with high pathogenicity avian influenza H5N1, clade 2.3.4.4b, in Germany, 2022
- Author
-
Martin Peters, Jacqueline King, Peter Wohlsein, Christian Grund, and Timm Harder
- Subjects
General Veterinary ,Influenza A Virus, H5N1 Subtype ,Virulence ,Influenza in Birds ,Animals ,Endothelial Cells ,General Medicine ,Columbidae ,Microbiology ,Antigens, Viral - Abstract
Despite the increasing frequency of avian influenza (AI) cases in wild birds in Europe during the last decade, doves and pigeons were not recognized to be part of the AI epidemiology. Here we describe a natural, lethal HPAIV infection of subtype H5N1, clade 2.3.4.4b, in a wood pigeon (Columba palumbus) in Germany, 2022. The animal was housed in a bird sanctuary that suffered an HPAI-outbreak with multiple bird species affected. The pigeon's post mortem findings were dominated by an acute lymphohistiocytic meningoencephalitis as well as neuronal necrosis in the grey matter of the cerebral hemispheres and in the brain stem. Influenza A viral antigen was associated to these alterations with a striking ependymal and periventricular distribution most probably indicating intraventicular liquorogenic spread of the virus. In addition, typical severe multifocal to coalescing necrotizing pancreatitis was evident. Occasionally, vascular endothelial cells showed an intense viral antigen staining. Examination of oropharyngeal and cloacal swabs and of various tissues by real-time RT-PCR corroborated systemic infection with highly pathogenic (HP) AIV of subtype H5N1. Viral loads soared in brain and pancreas samples. Full genome sequencing directly from brain tissue confirmed the assignment of the virus to clade 2.3.4.4b of the goose/Guangdong lineage bearing a polybasic hemagglutinin cleavage site. Our results demonstrate the principal susceptibility of wood pigeons to HPAIV H5N1 resulting in a sporadic infection. Considering the wide distribution and roaming of wild, feral, and racing pigeons with often close contact to humans, thorough investigation of suspected cases including pathological manifestation is advisable.
- Published
- 2022
45. Datenmodelle in Cloud-Plattformen
- Author
-
Timo Barth, Samuel Wenz, and Christian Grund
- Subjects
Electrical and Electronic Engineering ,Atomic and Molecular Physics, and Optics - Abstract
Cloud-Plattformen werden in der industriellen Anwendung immer relevanter. Sie dienen sowohl als Datenablage, nehmen jedoch zunehmend auch Modellierungs-, Strukturierungs- und Austauschaspekte, sowohl für Engineering- als auch für Live-Daten wahr. In diesem Beitrag wird eine praxisnahe Anwendung vorgestellt, mithilfe derer Ingenieure in der Lage sind, die stetig steigende Anzahl von Daten in der Cloud sinnvoll abzubilden. Vorlage bilden hierzu bestehende Strukturen in Planungs-(CAE) bzw. Engineering-Systemen der Automatisierungstechnik und des Anlagenbaus. Das hierfür entwickelte Werkzeug „VisualHierarchy Modeller“ wird durch die Autoren am Beispiel der Cloudplattform MindSphere der Siemens AG vorgestellt. Dabei werden im gesamten Beitrag Analogien zur klassischen Software- und Plattform-Entwicklung aufgezeigt, um die angewendeten Konzepte sinnvoll zu klassifizieren.
- Published
- 2020
46. Works councils and performance appraisals
- Author
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Dirk Sliwka, Christian Grund, and Krystina Titz
- Subjects
Longitudinal study ,business.industry ,media_common.quotation_subject ,05 social sciences ,Face (sociological concept) ,Accounting ,language.human_language ,German ,Work (electrical) ,restrict ,Human resource management ,0502 economics and business ,Institution ,language ,Business ,050207 economics ,Industrial relations ,050203 business & management ,media_common - Abstract
PurposeWe analyze the role of works councils for the use of performance appraisals (PA). We distinguish between the incidence of PA systems as intended by the firm and their actual implementation on the level of the individual employee.Design/methodology/approachWe draw on two complementary data sets. These are the German Linked Personnel Panel (LPP), which combines firm-based information with information provided by several of those employees, and the German Socio-Economic Panel (SOEP), which is a representative longitudinal study of persons living in Germany.FindingsWe find that works councils tend to promote rather than restrict PA. Employees working in establishments with a works council are more likely to face a formal PA procedure. Works councils also act as a transmission institution for the actual use of an existing PA system – i.e. among the firms that claim to implement PA for all their employees, the likelihood of their employees actually having regular appraisals is substantially larger when works councils are in place. Moreover, the existence of works councils is positively related particularly to PA systems, which affects bonus payments.Research limitations/implicationsWe contribute to the understanding of the work of works councils in firms. In more general, we shed light to the relation of industrial relations and human resource management in firms.Practical implicationsThis result hints at a higher acceptance of PA systems in firms with works councils. It seems likely that the stronger formalization of such systems necessitated by codetermination laws increases the likelihood of supervisors consistently carrying out such appraisals.Originality/valueWe are the first who complement the analysis of the existence of HR practices (PA system) with its actual use for employees.
- Published
- 2020
47. Antecedents of overtime work: The case of junior academics
- Author
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Irina Frei and Christian Grund
- Subjects
Working hours ,Organizational Behavior and Human Resource Management ,Labour economics ,education ,05 social sciences ,Public debate ,050301 education ,Overtime ,Overtime work ,Working time ,Political science ,0502 economics and business ,Part-time employment ,0503 education ,050203 business & management - Abstract
Despite the ongoing public debate about precarious working conditions in academia, there is only little evidence on working hours and overtime work for the group of (non-tenured) junior academics. We make use of unique longitudinal survey data on the occupational situation and careers of doctoral students and doctorate holders in science, technology, engineering and mathematics fields in Germany. We find that overtime hours are less pronounced among firm employees holding a doctorate and among postdocs than they are among doctoral students. This result is prevalent both between individuals in the cross-section and with regard to individual fixed effects panel estimations. In contrast to firm employees, overtime hours are in a considerable way positively associated with part-time contracts for doctoral students. Furthermore, our results reveal that individuals’ career orientation is positively associated with extra hours. In contrast, individuals with family responsibilities spend significantly fewer hours at work.
- Published
- 2020
48. Antigenic and Molecular Characterization of Virulent Newcastle Disease Viruses Circulating in Ethiopia Between 1976 and 2008
- Author
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Timm C. Harder, Berhe Gebreegziabher Tekola, Fufa D Bari, Christian Grund, Martin Beer, and Esayas Gelaye
- Subjects
animal structures ,antigenic ,Phylogenetic tree ,biology ,040301 veterinary sciences ,0402 animal and dairy science ,Embryonated ,Outbreak ,Virulence ,Research and Reports [Veterinary Medicine] ,04 agricultural and veterinary sciences ,biology.organism_classification ,fusion gene sequence ,040201 dairy & animal science ,Virology ,Newcastle disease ,Virus ,0403 veterinary science ,molecular characterization ,NDV ,velogenic ,Genotype ,pathogenicity ,Specific-pathogen-free ,Original Research - Abstract
Fufa D Bari,1,2 Esayas Gelaye,3 Berhe Gebreegziabher Tekola,3 Timm Harder,1 Martin Beer,1 Christian Grund1 1Institute of Infectology, Friedrich-Loeffler-Institut, Greifswald, Germany; 2Department of Microbiology, Immunology and Veterinary Public Health, College of Veterinary Medicine and Agriculture, Addis Ababa University, Bishoftu, Ethiopia; 3National Veterinary Institute, Bishoftu, EthiopiaCorrespondence: Fufa D BariDepartment of Microbiology, Immunology and Veterinary Public Health, College of Veterinary Medicine and Agriculture, Addis Ababa University, P O Box 34, Bishoftu, EthiopiaTel +251929190312Fax +251114339933Email fufa.dawo@aau.edu.etIntroduction: Newcastle disease virus (NDV) cultures held in the isolate collections in Ethiopia between 1976 and 2008 were not characterized using biological and molecular techniques. The already characterized NDV isolates belonged to genotype VI but the genetic nature of previously collected isolates, which could shade light on the history of introduction into the country and their evolutionary relationships, were not established.Methods: A total of 14 NDVs (11 obtained from outbreak cases in chickens and three commercial vaccinal strains used in the country) were inoculated into specific pathogen free (SPF) embryonated chicken eggs (ECE). Allantoic fluids harvested from grown SPF ECE were tested by heamagglutination (HA) and heamagglutination inhibition (HI) tests. Partial F gene sequences were generated for all samples and molecular evolutionary relationships were reconstructed together with reference sequences freely available online. The pathogenicities of the isolates were assessed in vivo by determining their intracerebral pathogenicity index (ICPI) in day-old chicks and molecularly by determination of F gene cleavage sites.Results: Of these, 12 viruses (two vaccines and 10 outbreaks) were successfully propagated as evidenced by a positive heamagglutination (HA) test. These 12 propagated viruses were further characterized by heamagglutination inhibition (HI) test, of which only three viruses reacted with monoclonal antibody (MAb 617/616) specific for pigeon paramyxovirus-1. In addition, all 14 viruses were characterized by partial fusion (F) gene sequencing and phylogenetic tree reconstruction. The Ethiopian NDV isolates clustered with genotype VI viruses, forming two clades (groups 1 and 2) that have ancestral relationships with Egypt-1990 and Sudan-1975 like viruses.Discussion: The characterized genotype VI NDVs were genetically similar to currently circulating NDVs in Ethiopia. The isolates had cleavage sites consistent with mesogenic/velogenic NDV with a mean ICPI value of 1.76, indicating that the isolates were velogenic. Two and four highly virulent viruses were thermostable at 56°C for 2 hours and 1 hour, respectively. To reduce chicken mortality and production losses, proper control of the disease should be instituted using high quality and protective vaccines together with strong biosecurity measures.Keywords: antigenic, NDV, fusion gene sequence, molecular characterization, pathogenicity, velogenic
- Published
- 2021
49. Genetic Characterization and Zoonotic Potential of Highly Pathogenic Avian Influenza Virus A(H5N6/H5N5), Germany, 2017–2018
- Author
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Jacqueline King, Susanne Koethe, Martin Beer, Daniela Hüssy, Anne Pohlmann, Reiner Ulrich, Simone Martina Meier, Timm C. Harder, Donata Hoffmann, Jan Schinköthe, Christian Grund, University of Zurich, and Beer, Martin
- Subjects
Epidemiology ,viruses ,Reassortment ,lcsh:Medicine ,Genetic Characterization and Zoonotic Potential of Highly Pathogenic Avian Influenza Virus A(H5N6/H5N5), Germany, 2017–2018 ,HPAI ,epizootic ,Poultry ,2726 Microbiology (medical) ,Disease Outbreaks ,0302 clinical medicine ,H5Nx ,Germany ,030212 general & internal medicine ,Clade ,High potential ,clade 2.3.4.4b ,Dispatch ,H5N6 ,H5N5 ,3. Good health ,Infectious Diseases ,Highly Pathogenic Avian Influenza Virus ,Influenza A virus ,ferret model ,influenza ,Microbiology (medical) ,030231 tropical medicine ,Animals, Wild ,610 Medicine & health ,Biology ,lcsh:Infectious and parasitic diseases ,Birds ,respiratory infections ,03 medical and health sciences ,Orthomyxoviridae Infections ,H5N8 ,medicine ,Animals ,lcsh:RC109-216 ,highly pathogenic avian influenza ,Poultry Diseases ,10082 Institute of Food Safety and Hygiene ,Epizootic ,lcsh:R ,Ferrets ,2725 Infectious Diseases ,Pathogenicity ,medicine.disease ,zoonotic potential ,Virology ,zoonoses ,Disease Models, Animal ,Influenza in Birds ,570 Life sciences ,biology ,reassortment ,2713 Epidemiology - Abstract
We genetically characterized highly pathogenic avian influenza virus A(H5N6) clade 2.3.4.4b isolates found in Germany in 2017–2018 and assessed pathogenicity of representative H5N5 and H5N6 viruses in ferrets. These viruses had low pathogenicity; however, continued characterization of related isolates is warranted because of their high potential for reassortment.
- Published
- 2019
50. Career interruptions and current remuneration
- Author
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Benedikt Gerst and Christian Grund
- Subjects
Organizational Behavior and Human Resource Management ,Strategy and Management ,media_common.quotation_subject ,Compensation (psychology) ,05 social sciences ,Wage ,Middle management ,Management of Technology and Innovation ,0502 economics and business ,Unemployment ,Remuneration ,Parental leave ,Demographic economics ,Salary ,Business ,050207 economics ,050203 business & management ,Gender pay gap ,media_common - Abstract
PurposeCareer interruptions of employees imply important issues for both firms and individuals, including a possibly lower compensation after returning to a job. Different compensation components are explored, as bonus payments frequently complement fixed salaries for many employees, making various channels of lower compensation possible. This paper aims to discuss this issue.Design/methodology/approachThis study is based on a yearly salary survey among a rather homogeneous group of professionals and middle managers from the German chemical sector, which contains detailed information on compensation components next to individual and job characteristics. The incidence and duration of past career interruptions act as the most important independent variables. Mincer-type wage regressions are complemented by estimations on wage increases.FindingsThe results show that career interruptions are more related to lower subsequent bonus payments than they are to fixed salaries. Furthermore, interruptions caused by unemployment are associated with higher interruption pay gaps than those resulting from other reasons such as parental leave. The results even hint for catch-up effects following parental leave with regard to higher wage increases compared to individuals without interruptions. Career interruptions are more prevalent for female managers offering an explanation for a considerable part of gender pay gaps. Wage losses after career interruptions are more pronounced for male employees than they are for females, though.Originality/valueThis study extents the literature by disentangling the relation of career interruptions and different compensation components, bonus payments next to fixed salaries in particular. The role of interruption type and gender are also taken into account so that the paper deepens the understanding of the role of past career interruptions for employees’ remuneration.
- Published
- 2019
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