Clinical outcome of Henipavirus infection in hamsters is determined by the route and dose of infection

Barry Rockx, Douglas Brining, Joshua Kramer, Julie Callison, Hideki Ebihara, Keith Mansfield, Heinz Feldmann

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Nipah virus (NiV) and Hendra virus (HeV) are emerging zoonotic viruses and the causative agents of severe respiratory disease and encephalitis in humans. Little is known about the mechanisms that govern the development of respiratory and neurological disease. Using a hamster model of lethal NiV and HeV infection, we describe the role of the route and dose of infection on the clinical outcome and determine virus tropism and host responses following infection. Infection of hamster with a high dose of NiV or HeV resulted in acute respiratory distress. NiV initially replicated in the upper respiratory tract epithelium, whereas HeV initiated infection primarily in the interstitium. In contrast, infection with a low dose of NiV or HeV resulted in the development of neurological signs and more systemic spread of the virus through involvement of the endothelium. The development of neurological signs coincided with disruption of the blood-brain barrier (BBB) and expression of tumor necrosis alpha (TNF-α) and interleukin 1 β (IL-1β). In addition, interferon-inducible protein 10 (IP-10) was identified as playing an important role in NiV and HeV pathogenesis. These studies reveal novel information on the development and progression of NiV and HeV clinical disease, provide a mechanism for the differences in transmission observed between NiV and HeV outbreaks, and identify specific cytokines and chemokines that serve as important targets for treatment.

Original languageEnglish (US)
Pages (from-to)7658-7671
Number of pages14
JournalJournal of virology
Volume85
Issue number15
DOIs
StatePublished - Aug 2011

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint Dive into the research topics of 'Clinical outcome of Henipavirus infection in hamsters is determined by the route and dose of infection'. Together they form a unique fingerprint.

Cite this