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A Novel Highly Reproducible and Lethal Nonhuman Primate Model for Orthopox Virus Infection

The intentional re-introduction of Variola virus (VARV), the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV) and Monkeypox virus (MPXV) cause severe diseases in humans. Smallpox vaccines presently av...

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Autores principales: Kramski, Marit, Mätz-Rensing, Kerstin, Stahl-Hennig, Christiane, Kaup, Franz-Josef, Nitsche, Andreas, Pauli, Georg, Ellerbrok, Heinz
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861679/
https://www.ncbi.nlm.nih.gov/pubmed/20454688
http://dx.doi.org/10.1371/journal.pone.0010412
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author Kramski, Marit
Mätz-Rensing, Kerstin
Stahl-Hennig, Christiane
Kaup, Franz-Josef
Nitsche, Andreas
Pauli, Georg
Ellerbrok, Heinz
author_facet Kramski, Marit
Mätz-Rensing, Kerstin
Stahl-Hennig, Christiane
Kaup, Franz-Josef
Nitsche, Andreas
Pauli, Georg
Ellerbrok, Heinz
author_sort Kramski, Marit
collection PubMed
description The intentional re-introduction of Variola virus (VARV), the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV) and Monkeypox virus (MPXV) cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus). A CPXV named calpox virus was isolated from a lethal orthopox virus (OPV) outbreak in New World monkeys. We demonstrated that marmosets infected with calpox virus, not only via the intravenous but also the intranasal route, reproducibly develop symptoms resembling smallpox in humans. Infected animals died within 1–3 days after onset of symptoms, even when very low infectious viral doses of 5×10(2) pfu were applied intranasally. Infectious virus was demonstrated in blood, saliva and all organs analyzed. We present the first characterization of a new OPV infection model inducing a disease in common marmosets comparable to smallpox in humans. Intranasal virus inoculation mimicking the natural route of smallpox infection led to reproducible infection. In vivo titration resulted in an MID(50) (minimal monkey infectious dose 50%) of 8.3×10(2) pfu of calpox virus which is approximately 10,000-fold lower than MPXV and VARV doses applied in the macaque models. Therefore, the calpox virus/marmoset model is a suitable nonhuman primate model for the validation of vaccines and antiviral drugs. Furthermore, this model can help study mechanisms of OPV pathogenesis.
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spelling pubmed-28616792010-05-07 A Novel Highly Reproducible and Lethal Nonhuman Primate Model for Orthopox Virus Infection Kramski, Marit Mätz-Rensing, Kerstin Stahl-Hennig, Christiane Kaup, Franz-Josef Nitsche, Andreas Pauli, Georg Ellerbrok, Heinz PLoS One Research Article The intentional re-introduction of Variola virus (VARV), the agent of smallpox, into the human population is of great concern due its bio-terroristic potential. Moreover, zoonotic infections with Cowpox (CPXV) and Monkeypox virus (MPXV) cause severe diseases in humans. Smallpox vaccines presently available can have severe adverse effects that are no longer acceptable. The efficacy and safety of new vaccines and antiviral drugs for use in humans can only be demonstrated in animal models. The existing nonhuman primate models, using VARV and MPXV, need very high viral doses that have to be applied intravenously or intratracheally to induce a lethal infection in macaques. To overcome these drawbacks, the infectivity and pathogenicity of a particular CPXV was evaluated in the common marmoset (Callithrix jacchus). A CPXV named calpox virus was isolated from a lethal orthopox virus (OPV) outbreak in New World monkeys. We demonstrated that marmosets infected with calpox virus, not only via the intravenous but also the intranasal route, reproducibly develop symptoms resembling smallpox in humans. Infected animals died within 1–3 days after onset of symptoms, even when very low infectious viral doses of 5×10(2) pfu were applied intranasally. Infectious virus was demonstrated in blood, saliva and all organs analyzed. We present the first characterization of a new OPV infection model inducing a disease in common marmosets comparable to smallpox in humans. Intranasal virus inoculation mimicking the natural route of smallpox infection led to reproducible infection. In vivo titration resulted in an MID(50) (minimal monkey infectious dose 50%) of 8.3×10(2) pfu of calpox virus which is approximately 10,000-fold lower than MPXV and VARV doses applied in the macaque models. Therefore, the calpox virus/marmoset model is a suitable nonhuman primate model for the validation of vaccines and antiviral drugs. Furthermore, this model can help study mechanisms of OPV pathogenesis. Public Library of Science 2010-04-29 /pmc/articles/PMC2861679/ /pubmed/20454688 http://dx.doi.org/10.1371/journal.pone.0010412 Text en Kramski et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kramski, Marit
Mätz-Rensing, Kerstin
Stahl-Hennig, Christiane
Kaup, Franz-Josef
Nitsche, Andreas
Pauli, Georg
Ellerbrok, Heinz
A Novel Highly Reproducible and Lethal Nonhuman Primate Model for Orthopox Virus Infection
title A Novel Highly Reproducible and Lethal Nonhuman Primate Model for Orthopox Virus Infection
title_full A Novel Highly Reproducible and Lethal Nonhuman Primate Model for Orthopox Virus Infection
title_fullStr A Novel Highly Reproducible and Lethal Nonhuman Primate Model for Orthopox Virus Infection
title_full_unstemmed A Novel Highly Reproducible and Lethal Nonhuman Primate Model for Orthopox Virus Infection
title_short A Novel Highly Reproducible and Lethal Nonhuman Primate Model for Orthopox Virus Infection
title_sort novel highly reproducible and lethal nonhuman primate model for orthopox virus infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2861679/
https://www.ncbi.nlm.nih.gov/pubmed/20454688
http://dx.doi.org/10.1371/journal.pone.0010412
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