Development of an acute and highly pathogenic nonhuman primate model of nipah virus infection

Thomas Geisbert, Kathleen M. Daddario-Dicaprio, Andrew C. Hickey, Mark A. Smith, Yee Peng Chan, Lin Fa Wang, Joseph J. Mattapallil, Joan B. Geisbert, Katharine N. Bossart, Christopher C. Broder

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Nipah virus (NiV) is an enigmatic emerging pathogen that causes severe and often fatal neurologic and/or respiratory disease in both animals and humans. Amongst people, case fatality rates range between 40 and 75 percent and there are no vaccines or treatments approved for human use. Guinea pigs, hamsters, cats, ferrets, pigs and most recently squirrel monkeys (New World monkey) have been evaluated as animal models of human NiV infection, and with the exception of the ferret, no model recapitulates all aspects of NiV-mediated disease seen in humans. To identify a more viable nonhuman primate (NHP) model, we examined the pathogenesis of NiV in African green monkeys (AGM). Exposure of eight monkeys to NiV produced a severe systemic infection in all eight animals with seven of the animals succumbing to infection. Viral RNA was detected in the plasma of challenged animals and occurred in two of three subjects as a peak between days 7 and 21, providing the first clear demonstration of plasma-associated viremia in NiV experimentally infected animals and suggested a progressive infection that seeded multiple organs simultaneously from the initial site of virus replication. Unlike the cat, hamster and squirrel monkey models of NiV infection, severe respiratory pathology, neurological disease and generalized vasculitis all manifested in NiV-infected AGMs, providing an accurate reflection of what is observed in NiV-infected humans. Our findings demonstrate the first consistent and highly pathogenic NHP model of NiV infection, providing a new and critical platform in the evaluation and licensure of either passive and active immunization or therapeutic strategies for human use.

Original languageEnglish (US)
Article numbere10690
JournalPLoS One
Volume5
Issue number5
DOIs
StatePublished - 2010
Externally publishedYes

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Nipah Virus
Nipah virus
Virus Diseases
Viruses
Primates
animal models
infection
Animals
Saimiri
Ferrets
ferrets
animals
hamsters
Cricetinae
immunization
Cats
Infection
Platyrrhini
cats
Cercopithecus aethiops

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Geisbert, T., Daddario-Dicaprio, K. M., Hickey, A. C., Smith, M. A., Chan, Y. P., Wang, L. F., ... Broder, C. C. (2010). Development of an acute and highly pathogenic nonhuman primate model of nipah virus infection. PLoS One, 5(5), [e10690]. https://doi.org/10.1371/journal.pone.0010690

Development of an acute and highly pathogenic nonhuman primate model of nipah virus infection. / Geisbert, Thomas; Daddario-Dicaprio, Kathleen M.; Hickey, Andrew C.; Smith, Mark A.; Chan, Yee Peng; Wang, Lin Fa; Mattapallil, Joseph J.; Geisbert, Joan B.; Bossart, Katharine N.; Broder, Christopher C.

In: PLoS One, Vol. 5, No. 5, e10690, 2010.

Research output: Contribution to journalArticle

Geisbert, T, Daddario-Dicaprio, KM, Hickey, AC, Smith, MA, Chan, YP, Wang, LF, Mattapallil, JJ, Geisbert, JB, Bossart, KN & Broder, CC 2010, 'Development of an acute and highly pathogenic nonhuman primate model of nipah virus infection', PLoS One, vol. 5, no. 5, e10690. https://doi.org/10.1371/journal.pone.0010690
Geisbert, Thomas ; Daddario-Dicaprio, Kathleen M. ; Hickey, Andrew C. ; Smith, Mark A. ; Chan, Yee Peng ; Wang, Lin Fa ; Mattapallil, Joseph J. ; Geisbert, Joan B. ; Bossart, Katharine N. ; Broder, Christopher C. / Development of an acute and highly pathogenic nonhuman primate model of nipah virus infection. In: PLoS One. 2010 ; Vol. 5, No. 5.
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