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      Dynamics of Pathological and Virological Findings During Experimental Calpox Virus Infection of Common Marmosets ( Callithrix jacchus)

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          Abstract

          Experimental intranasal infection of marmosets ( Callithrix jacchus) with calpox virus results in fatal disease. Route and dose used for viral inoculation of the test animals mimics the natural transmission of smallpox, thus representing a suitable model to study pathogenesis and to evaluate new vaccines against orthopoxvirus infection. However, the pathogenic mechanisms leading to death are still unclear. Therefore, our study aimed at investigating the kinetics of pathological alterations to clarify the pathogenesis in calpox virus infection. Following intranasal inoculation with two different viral doses, common marmosets were sacrificed on days 3, 5, 7, 10 and 12 post inoculation. Collected tissue was screened using histopathology, immunohistochemistry, transmission electron microscopy, and virological assays. Our data suggest that primary replication took place in nasal and bronchial epithelia followed by secondary replication in submandibular lymph nodes and spleen. Parallel to viremia at day 7, virus was detectable in many organs, mainly located in epithelial cells and macrophages, as well as in endothelial cells. Based on the onset of clinical signs, the histological and ultrastructural lesions and the immunohistochemical distribution pattern of the virus, the incubation period was defined to last 11 days, which resembles human smallpox. In conclusion, the data indicate that the calpox model is highly suitable for studying orthopoxvirus-induced disease.

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          Most cited references78

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          The detection of monkeypox in humans in the Western Hemisphere.

          During May and June 2003, an outbreak of febrile illness with vesiculopustular eruptions occurred among persons in the midwestern United States who had had contact with ill pet prairie dogs obtained through a common distributor. Zoonotic transmission of a bacterial or viral pathogen was suspected. We reviewed medical records, conducted interviews and examinations, and collected blood and tissue samples for analysis from 11 patients and one prairie dog. Histopathological and electron-microscopical examinations, microbiologic cultures, and molecular assays were performed to identify the etiologic agent. The initial Wisconsin cases evaluated in this outbreak occurred in five males and six females ranging in age from 3 to 43 years. All patients reported having direct contact with ill prairie dogs before experiencing a febrile illness with skin eruptions. We found immunohistochemical or ultrastructural evidence of poxvirus infection in skin-lesion tissue from four patients. Monkeypox virus was recovered in cell cultures of seven samples from patients and from the prairie dog. The virus was identified by detection of monkeypox-specific DNA sequences in tissues or isolates from six patients and the prairie dog. Epidemiologic investigation suggested that the prairie dogs had been exposed to at least one species of rodent recently imported into the United States from West Africa. Our investigation documents the isolation and identification of monkeypox virus from humans in the Western Hemisphere. Infection of humans was associated with direct contact with ill prairie dogs that were being kept or sold as pets. Copyright 2004 Massachusetts Medical Society
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            Poxviruses and immune evasion.

            Large DNA viruses defend against hostile assault executed by the host immune system by producing an array of gene products that systematically sabotage key components of the inflammatory response. Poxviruses target many of the primary mediators of innate immunity including interferons, tumor necrosis factors, interleukins, complement, and chemokines. Poxviruses also manipulate a variety of intracellular signal transduction pathways such as the apoptotic response. Many of the poxvirus genes that disrupt these pathways have been hijacked directly from the host immune system, while others have demonstrated no clear resemblance to any known host genes. Nonetheless, the immunological targets and the diversity of strategies used by poxviruses to disrupt these host pathways have provided important insights into diverse aspects of immunology, virology, and inflammation. Furthermore, because of their anti-inflammatory nature, many of these poxvirus proteins hold promise as potential therapeutic agents for acute or chronic inflammatory conditions.
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              Zoonotic poxviruses

              Poxviruses compromise a group of long known important pathogens including some zoonotic members affecting lifestock animals and humans. While whole genome sequence analysis started to shed light into the molecular mechanisms underlying host cell infection, viral replication as well as virulence, our understanding of poxvirus maintenance in nature and their transmission to humans is still poor. During the last two decades, reports on emerging human monkeypox outbreaks in Africa and North America, the increasing number of cowpox virus infections in cats, exotic animals and humans and cases of vaccinia virus infections in humans in South America and India reminded us that – beside the eradicated smallpox virus – there are other poxviruses that can cause harm to men. We start to learn that the host range of some poxviruses is way broader than initially thought and that mainly rodents seem to function as virus reservoir. The following review is aiming to provide an up-to-date overview on the epidemiology of zoonotic poxviruses, emphasizing orthopoxviruses. By outlining the current knowledge of poxvirus transmission, we hope to raise the awareness about modes of acquisition of infections and their proper diagnosis.
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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                28 November 2017
                December 2017
                : 9
                : 12
                : 363
                Affiliations
                [1 ]Pathology Unit, German Primate Center (DPZ), Kellnerweg 4, 37077 Göttingen, Germany; Anne.Schmitt@ 123456bfr.bund.de (A.S.); fkaup@ 123456gwdg.de (F.-J.K.)
                [2 ]Unit of Infection Models, German Primate Center (DPZ), Kellnerweg 4, 37077 Göttingen, Germany; LGan@ 123456dpz.eu (L.L.G.); qinqin99413@ 123456googlemail.com (T.S.); stahlh@ 123456dpz.eu (C.S.-H.)
                [3 ]Division of Microbiology and Animal Hygiene, Department of Animal Sciences, University of Göttingen, Burckhardtweg 2, 37077 Göttingen, Germany; abdelwahed@ 123456gwdg.de
                [4 ]Robert Koch-Institute, Centre for Biological Threats and Special Pathogens, Highly Pathogenic Viruses (ZBS1), Seestr. 10, 13353 Berlin, Germany; EllerbrokH@ 123456rki.de
                Author notes
                [* ]Correspondence: kmaetz@ 123456dpz.eu ; Tel.: +49-551-3851-386; Fax: +49-551-3851-442
                [†]

                These authors contributed equally to this work.

                Article
                viruses-09-00363
                10.3390/v9120363
                5744138
                29182537
                adfeeae5-145c-4a70-a328-c7f296c25caf
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 October 2017
                : 20 November 2017
                Categories
                Article

                Microbiology & Virology
                calpox virus,common marmoset,immunohistochemistry,nonhuman primate,orthopoxvirus,pathogenesis,transmission electron microscopy,virus infection

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