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

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 vacc...

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Main Authors: Anne Schmitt, Li Lin Gan, Ahmed Abd El Wahed, Tingchuan Shi, Heinz Ellerbrok, Franz-Josef Kaup, Christiane Stahl-Hennig, Kerstin Mätz-Rensing
Format: Article
Language:English
Published: MDPI AG 2017-11-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/9/12/363
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author Anne Schmitt
Li Lin Gan
Ahmed Abd El Wahed
Tingchuan Shi
Heinz Ellerbrok
Franz-Josef Kaup
Christiane Stahl-Hennig
Kerstin Mätz-Rensing
author_facet Anne Schmitt
Li Lin Gan
Ahmed Abd El Wahed
Tingchuan Shi
Heinz Ellerbrok
Franz-Josef Kaup
Christiane Stahl-Hennig
Kerstin Mätz-Rensing
author_sort Anne Schmitt
collection DOAJ
description 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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spelling doaj.art-4eed9e3821a9477f856d14e280d8775e2022-12-21T17:13:28ZengMDPI AGViruses1999-49152017-11-0191236310.3390/v9120363v9120363Dynamics of Pathological and Virological Findings During Experimental Calpox Virus Infection of Common Marmosets (Callithrix jacchus)Anne Schmitt0Li Lin Gan1Ahmed Abd El Wahed2Tingchuan Shi3Heinz Ellerbrok4Franz-Josef Kaup5Christiane Stahl-Hennig6Kerstin Mätz-Rensing7Pathology Unit, German Primate Center (DPZ), Kellnerweg 4, 37077 Göttingen, GermanyUnit of Infection Models, German Primate Center (DPZ), Kellnerweg 4, 37077 Göttingen, GermanyDivision of Microbiology and Animal Hygiene, Department of Animal Sciences, University of Göttingen, Burckhardtweg 2, 37077 Göttingen, GermanyUnit of Infection Models, German Primate Center (DPZ), Kellnerweg 4, 37077 Göttingen, GermanyRobert Koch-Institute, Centre for Biological Threats and Special Pathogens, Highly Pathogenic Viruses (ZBS1), Seestr. 10, 13353 Berlin, GermanyPathology Unit, German Primate Center (DPZ), Kellnerweg 4, 37077 Göttingen, GermanyUnit of Infection Models, German Primate Center (DPZ), Kellnerweg 4, 37077 Göttingen, GermanyPathology Unit, German Primate Center (DPZ), Kellnerweg 4, 37077 Göttingen, GermanyExperimental 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.https://www.mdpi.com/1999-4915/9/12/363calpox viruscommon marmosetimmunohistochemistrynonhuman primateorthopoxviruspathogenesistransmission electron microscopyvirus infection
spellingShingle Anne Schmitt
Li Lin Gan
Ahmed Abd El Wahed
Tingchuan Shi
Heinz Ellerbrok
Franz-Josef Kaup
Christiane Stahl-Hennig
Kerstin Mätz-Rensing
Dynamics of Pathological and Virological Findings During Experimental Calpox Virus Infection of Common Marmosets (Callithrix jacchus)
Viruses
calpox virus
common marmoset
immunohistochemistry
nonhuman primate
orthopoxvirus
pathogenesis
transmission electron microscopy
virus infection
title Dynamics of Pathological and Virological Findings During Experimental Calpox Virus Infection of Common Marmosets (Callithrix jacchus)
title_full Dynamics of Pathological and Virological Findings During Experimental Calpox Virus Infection of Common Marmosets (Callithrix jacchus)
title_fullStr Dynamics of Pathological and Virological Findings During Experimental Calpox Virus Infection of Common Marmosets (Callithrix jacchus)
title_full_unstemmed Dynamics of Pathological and Virological Findings During Experimental Calpox Virus Infection of Common Marmosets (Callithrix jacchus)
title_short Dynamics of Pathological and Virological Findings During Experimental Calpox Virus Infection of Common Marmosets (Callithrix jacchus)
title_sort dynamics of pathological and virological findings during experimental calpox virus infection of common marmosets callithrix jacchus
topic calpox virus
common marmoset
immunohistochemistry
nonhuman primate
orthopoxvirus
pathogenesis
transmission electron microscopy
virus infection
url https://www.mdpi.com/1999-4915/9/12/363
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