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Almut Prkno, Matthias Kaiser, Daniela Goerigk, Martin Pfeffer, Thomas W Vahlenkamp, Donata Hoffmann, Martin Beer, Alexander Starke
Cowpox virus (CPXV) infection is a reportable and potentially zoonotic disease that occurs sporadically in a variety of animals. During the past six decades, CPXV infection has been extensively researched and described in both domestic (cat, dog, horse, cattle) and zoo animals (e. g. elephant, rhinoceros, okapi). Of note, a review of the literature produced only three reports of CPXV in individual or small groups of South American camelids. The goal of this review was to describe the current knowledge as it relates to clinical features of CPXV infection in South American camelids and to compare the clinical manifestations with those described in other animal species...
February 2018: Tierärztliche Praxis. Ausgabe G, Grosstiere/Nutztiere
Iliana Georgana, Rebecca P Sumner, Greg J Towers, Carlos Maluquer de Motes
Cytosolic recognition of DNA has emerged as a critical cellular mechanism of host immune activation upon pathogen invasion. The central cytosolic DNA sensor cGAS activates STING, which is phosphorylated, dimerises and translocates from the ER to a perinuclear region to mediate IRF-3 activation. Poxviruses are dsDNA viruses replicating in the cytosol and hence likely to trigger cytosolic DNA sensing. Here we investigated the activation of innate immune signalling by 4 different strains of the prototypic poxvirus vaccinia virus (VACV) in a cell line proficient in DNA sensing...
February 28, 2018: Journal of Virology
Gianguglielmo Zehender, Alessia Lai, Carla Veo, Annalisa Bergna, Massimo Ciccozzi, Massimo Galli
Variola virus (VARV), the causative agent of smallpox, is an exclusively human virus belonging to the genus Orthopoxvirus, which includes many other viral species covering a wide range of mammal hosts, such as vaccinia, cowpox, camelpox, taterapox, ectromelia and monkeypox virus. The tempo and mode of evolution of Orthopoxviruses were reconstructed using a Bayesian phylodynamic framework by analysing 80 hemagglutinin sequences retrieved from public databases. Bayesian phylogeography was used to estimate their putative ancestral hosts...
February 15, 2018: Journal of Medical Virology
Elvin J Lauron, Liping Yang, Jabari I Elliott, Maria D Gainey, Daved H Fremont, Wayne M Yokoyama
Viruses have evolved mechanisms of MHCI inhibition in order to evade recognition by cytotoxic CD8+ T cells (CTLs), which is well-illustrated by our prior studies on cowpox virus (CPXV) that encodes potent MHCI inhibitors. Deletion of CPXV viral MHCI inhibitors markedly attenuated in vivo infection due to effects on CTL effector function, not priming. However, the CTL response to CPXV in C57BL/6 mice is dominated by a single peptide antigen presented by H-2Kb. Here we evaluated the effect of viral MHCI inhibition on immunodominant (IDE) and subdominant epitopes (SDE) as this has not been thoroughly examined...
February 2018: PLoS Pathogens
Yana Khlusevich, Andrey Matveev, Ivan Baykov, Leonid Bulychev, Nikolai Bormotov, Ivan Ilyichev, Georgiy Shevelev, Vera Morozova, Dmitrii Pyshnyi, Nina Tikunova
In this study, five phage display antibodies (pdAbs) against ectromelia virus (ECTV) were selected from vaccinia virus (VACV)-immune phage-display library of human single chain variable fragments (scFv). ELISA demonstrated that selected pdAbs could recognize ECTV, VACV, and cowpox virus (CPXV). Atomic force microscopy visualized binding of the pdAbs to VACV. Three of the selected pdAbs neutralized variola virus (VARV) in the plaque reduction neutralization test. Western blot analysis of ECTV, VARV, VACV, and CPXV proteins indicated that neutralizing pdAbs bound orthopoxvirus 35 kDa proteins, which are encoded by the open reading frames orthologous to the ORF H3L in VACV...
February 7, 2018: Antiviral Research
N Jungwirth, C Puff, K Köster, R Mischke, H Meyer, A Stark, B Thoma, G Zöller, F Seehusen, M Hewicker-Trautwein, A Beineke, W Baumgärtner, P Wohlsein
Within 4 weeks, five cats with skin lesions affecting the hindlimbs and mainly consisting of oedema, hyperaemia and plaque-like alterations were presented to the same veterinary clinic. The cats were suffering from lameness, trauma, renal insufficiency or complicated tail amputation. Although the lesions seemed unusual for a poxvirus infection, microscopical examination of biopsy samples or specimens taken during necropsy examination revealed ballooning degeneration of keratinocytes with eosinophilic, cytoplasmic inclusion bodies indicative of an orthopoxvirus infection...
January 2018: Journal of Comparative Pathology
Marica Grossegesse, Joerg Doellinger, Annemarie Fritsch, Michael Laue, Janett Piesker, Lars Schaade, Andreas Nitsche
The emergence of Variola virus-like viruses by natural evolution of zoonotic Orthopoxviruses, like Cowpox virus (CPXV), is a global health threat. The proteasome is essential for poxvirus replication, making the viral components interacting with the ubiquitin-proteasome system attractive antiviral targets. We show that proteasome inhibition impairs CPXV replication by prevention of uncoating, suggesting that uncoating is mediated by proteasomal degradation of viral core proteins. Although Orthopoxvirus particles contain considerable amounts of ubiquitin, distinct modification sites are largely unknown...
January 29, 2018: Scientific Reports
Lotte Spel, Rutger D Luteijn, Jan W Drijfhout, Stefan Nierkens, Marianne Boes, Emmanuel J H Wiertz
Viruses may interfere with the MHC class I antigen presentation pathway in order to avoid CD8+ T cell-mediated immunity. A key target within this pathway is the peptide transporter TAP. This transporter plays a central role in MHC class I-mediated peptide presentation of endogenous antigens. In addition, TAP plays a role in antigen cross-presentation of exogenously derived antigens by dendritic cells (DCs). In this study, a soluble form of the cowpox virus TAP inhibitor CPXV012 is synthesized for exogenous delivery into the antigen cross-presentation route of human monocyte-derived (mo)DCs...
October 19, 2017: Immunology and Cell Biology
Ewa Talarek, Magdalena Marczynska
An 11-year-old girl presented to the hospital with a skin lesion on her left cheek that had been present for 3 weeks. She lived in a suburban area in Poland and had direct contact with cats that lived in her home and roamed freely; no bites or scratches were reported. Her parents reported that..
January 11, 2018: New England Journal of Medicine
Robert Koban, Markus Neumann, Aila Daugs, Oliver Bloch, Andreas Nitsche, Stefan Langhammer, Heinz Ellerbrok
Gefitinib is a specific inhibitor of the epidermal growth factor receptor (EGFR) and FDA approved for treatment of non-small cell lung cancer. In a previous study we could show the in vitro efficacy of gefitinib for treatment of poxvirus infections in monolayer (2D) cultivated cell lines. Permanent cell lines and 2D cultures, however, are known to be rather unphysiological; therefore it is difficult to predict whether determined effective concentrations or the drug efficacy per se are transferable to the in vivo situation...
February 2018: Antiviral Research
Ines Eder, Patrick Vollmar, Martin Pfeffer, Philipp Naether, Arne Christian Rodloff, Hermann Meyer
Here we present two cases of human infection with cowpox virus with distinct clinical courses. A series of clinical photographs documents lesion progression over time. In the first case-an unvaccinated young veterinary assistant-a pustule was treated locally with cortisone. The lesion turned into a large ulcer accompanied by severe lymphadenitis. Based on her close contact to a sick stray cat, infection with cowpox virus was assumed and confirmed by virus isolation, PCR, and serology. The clinical course took up to eleven months until healing of the wound was complete...
December 7, 2017: Viruses
Almut Prkno, Donata Hoffmann, Daniela Goerigk, Matthias Kaiser, Anne Catherine Franscisca van Maanen, Kathrin Jeske, Maria Jenckel, Florian Pfaff, Thomas W Vahlenkamp, Martin Beer, Rainer G Ulrich, Alexander Starke, Martin Pfeffer
Four cowpox virus (CPXV) outbreaks occurred in unrelated alpaca herds in Eastern Germany during 2012-2017. All incidents were initially noticed due to severe, generalized, and finally lethal CPXV infections, which were confirmed by testing of tissue and serum samples. As CPXV-infection has been described in South American camelids (SACs) only three times, all four herds were investigated to gain a deeper understanding of CPXV epidemiology in alpacas. The different herds were investigated twice, and various samples (serum, swab samples, and crusts of suspicious pox lesions, feces) were taken to identify additionally infected animals...
November 18, 2017: Viruses
José Esparza, Livia Schrick, Clarissa R Damaso, Andreas Nitsche
For almost 150 years after Edward Jenner had published the "Inquiry" in 1798, it was generally assumed that the cowpox virus was the vaccine against smallpox. It was not until 1939 when it was shown that vaccinia, the smallpox vaccine virus, was serologically related but different from the cowpox virus. In the absence of a known natural host, vaccinia has been considered to be a laboratory virus that may have originated from mutational or recombinational events involving cowpox virus, variola viruses or some unknown ancestral Orthopoxvirus...
December 19, 2017: Vaccine
Marica Grossegesse, Joerg Doellinger, Alona Tyshaieva, Lars Schaade, Andreas Nitsche
DNA viruses, like poxviruses, possess a highly stable genome, suggesting that adaptation of virus particles to specific cell types is not restricted to genomic changes. Cowpox viruses are zoonotic poxviruses with an extraordinarily broad host range, demonstrating their adaptive potential in vivo. To elucidate adaptation mechanisms of poxviruses, we isolated cowpox virus particles from a rat and passaged them five times in a human and a rat cell line. Subsequently, we analyzed the proteome and genome of the non-passaged virions and each passage...
November 10, 2017: Viruses
Julia Stagegaard, Andreas Kurth, Daniel Stern, Piotr Wojciech Dabrowski, Ann Pocknell, Andreas Nitsche, Livia Schrick
Cowpox virus infections in captive cheetahs (Acinonyx jubatus) with high morbidity and mortality have already been reported in the UK and Russia in the 1970s. However, most of the reported cases have been singular events. Here, we report a total of five cowpox virus outbreaks in cheetahs in the same safari park in Denmark between 2010 and 2014. Nine cheetahs showed varying severity of clinical disease; two of them died (22%). All episodes occurred between August and October of the respective year. No other carnivores kept at the same institution nor the keepers taking care of the animals were clinically affected...
2017: PloS One
Jiangan Xie, Yongqun He
Vaccine is the one of the greatest inventions of modern medicine that has contributed most to the relief of human misery and the exciting increase in life expectancy. In 1796, an English country physician, Edward Jenner, discovered that inoculating mankind with cowpox can protect them from smallpox (Riedel S, Edward Jenner and the history of smallpox and vaccination. Proceedings (Baylor University. Medical Center) 18(1):21, 2005). Based on the vaccination worldwide, we finally succeeded in the eradication of smallpox in 1977 (Henderson, Vaccine 29:D7-D9, 2011)...
2017: Advances in Experimental Medicine and Biology
Marica Grossegesse, Joerg Doellinger, Berit Haldemann, Lars Schaade, Andreas Nitsche
Transcripts are known to be incorporated in particles of DNA viruses belonging to the families of Herpesviridae and Mimiviridae, but the presence of transcripts in other DNA viruses, such as poxviruses, has not been analyzed yet. Therefore, we first established a next-generation-sequencing (NGS)-based protocol, enabling the unbiased identification of transcripts in virus particles. Subsequently, we applied our protocol to analyze RNA in an emerging zoonotic member of the Poxviridae family, namely Cowpox virus...
October 13, 2017: Viruses
Giusy Cardeti, Cesare Ernesto Maria Gruber, Claudia Eleni, Fabrizio Carletti, Concetta Castilletti, Giuseppe Manna, Francesca Rosone, Emanuela Giombini, Marina Selleri, Daniele Lapa, Vincenzo Puro, Antonino Di Caro, Raniero Lorenzetti, Maria Teresa Scicluna, Goffredo Grifoni, Annapaola Rizzoli, Valentina Tagliapietra, Lorenzo De Marco, Maria Rosaria Capobianchi, Gian Luca Autorino
In January 2015, during a 3-week period, 12 captive Tonkean macacques at a sanctuary in Italy died. An orthopoxvirus infection was suspected because of negative-staining electron microscopy results. The diagnosis was confirmed by histology, virus isolation, and molecular analysis performed on different organs from all animals. An epidemiologic investigation was unable to define the infection source in the surrounding area. Trapped rodents were negative by virologic testing, but specific IgG was detected in 27...
December 2017: Emerging Infectious Diseases
Marine Ricordel, Johann Foloppe, Christelle Pichon, Nathalie Sfrontato, Delphine Antoine, Caroline Tosch, Sandrine Cochin, Pascale Cordier, Eric Quemeneur, Christelle Camus-Bouclainville, Stéphane Bertagnoli, Philippe Erbs
Oncolytic virus therapy has recently been recognized as a promising new therapeutic approach for cancer treatment. In this study, we are proposing for the first time to evaluate the in vitro and in vivo oncolytic capacities of the Cowpox virus (CPXV). To improve the tumor selectivity and oncolytic activity, we developed a thymidine kinase (TK)-deleted CPXV expressing the suicide gene FCU1, which converts the non-toxic prodrug 5-fluorocytosine (5-FC) into cytotoxic 5-fluorouracil (5-FU) and 5-fluorouridine-5'-monophosphate (5-FUMP)...
December 15, 2017: Molecular Therapy Oncolytics
Chad Smithson, Jacob Imbery, Chris Upton
We report a major improvement to the assembly of published short read sequencing data from an ancient variola virus (VARV) genome by the removal of contig-capping sequencing tags and manual searches for gap-spanning reads. The new assembly, together with camelpox and taterapox genomes, permitted new dates to be calculated for the last common ancestor of all VARV genomes. The analysis of recently sequenced VARV-like cowpox virus genomes showed that single nucleotide polymorphisms (SNPs) and amino acid changes in the vaccinia virus (VACV)-Cop-O1L ortholog, predicted to be associated with VARV host specificity and virulence, were introduced into the lineage before the divergence of these viruses...
September 8, 2017: Viruses
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