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2010-04-29Zeitschriftenartikel DOI: 10.1371/journal.pone.0010412
A Novel Highly Reproducible and Lethal Nonhuman Primate Model for Orthopox Virus Infection
dc.contributor.authorKramski, Marit
dc.contributor.authorMätz-Rensing, Kerstin
dc.contributor.authorStahl-Hennig, Christiane
dc.contributor.authorKaup, Franz-Josef
dc.contributor.authorNitsche, Andreas
dc.contributor.authorPauli, Georg
dc.contributor.authorEllerbrok, Heinz
dc.date.accessioned2018-05-07T13:51:25Z
dc.date.available2018-05-07T13:51:25Z
dc.date.created2010-05-11
dc.date.issued2010-04-29none
dc.identifier.otherhttp://edoc.rki.de/oa/articles/reG1y3vcsXk/PDF/28PshPZdQvJBo.pdf
dc.identifier.urihttp://edoc.rki.de/176904/633
dc.description.abstractThe 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 56102 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 MID50 (minimal monkey infectious dose 50%) of 8.36102 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.eng
dc.language.isoeng
dc.publisherRobert Koch-Institut, Infektionskrankheiten / Erreger
dc.subjectAnimalseng
dc.subjectCallithrixeng
dc.subjectCowpox viruseng
dc.subjectDisease Models Animaleng
dc.subjectOrthopoxvirus/pathogenicityeng
dc.subjectPoxviridae Infectionseng
dc.subjectSmallpox Vaccineeng
dc.subjectSurvival Rateeng
dc.subject.ddc610 Medizin
dc.titleA Novel Highly Reproducible and Lethal Nonhuman Primate Model for Orthopox Virus Infection
dc.typeperiodicalPart
dc.identifier.urnurn:nbn:de:0257-1008524
dc.identifier.doi10.1371/journal.pone.0010412
dc.identifier.doihttp://dx.doi.org/10.25646/558
local.edoc.container-titlePLoS One
local.edoc.fp-subtypeArtikel
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttp://www.plosone.org
local.edoc.container-publisher-namePublic Library of Science
local.edoc.container-volume5
local.edoc.container-issue4
local.edoc.container-year2010

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