Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques

David Safronetz, Joseph Prescott, Friederike Feldmann, Elaine Haddock, Rebecca Rosenke, Atsushi Okumura, Douglas Brining, Eric Dahlstrom, Stephen F. Porcella, Hideki Ebihara, Dana P. Scott, Brian Hjelle, Heinz Feldmann

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33 Scopus citations

Abstract

The pathophysiology of hantavirus pulmonary syndrome (HPS) remains unclear because of a lack of surrogate disease models with which to perform pathogenesis studies. Nonhuman primates (NHP) are considered the gold standard model for studying the underlying immune activation/suppression associated with immunopathogenic viruses such as hantaviruses; however, to date an NHP model for HPS has not been described. Here we show that rhesus macaques infected with Sin Nombre virus (SNV), the primary etiological agent of HPS in North America, propagated in deer mice develop HPS, which is characterized by thrombocytopenia, leukocytosis, and rapid onset of respiratory distress caused by severe interstitial pneumonia. Despite establishing a systemic infection, SNV differentially activated host responses exclusively in the pulmonary endothelium, potentially the mechanism leading to acute severe respiratory distress. This study presents a unique chronological characterization of SNV infection and provides mechanistic data into the pathophysiology of HPS in a closely related surrogate animal model. We anticipate this model will advance our understanding of HPS pathogenesis and will greatly facilitate research toward the development of effective therapeutics and vaccines against hantaviral diseases.

Original languageEnglish (US)
Pages (from-to)7114-7119
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number19
DOIs
StatePublished - May 13 2014

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Keywords

  • Disease modeling
  • Emerging pathogen
  • New World hantaviruses

ASJC Scopus subject areas

  • General

Cite this

Safronetz, D., Prescott, J., Feldmann, F., Haddock, E., Rosenke, R., Okumura, A., Brining, D., Dahlstrom, E., Porcella, S. F., Ebihara, H., Scott, D. P., Hjelle, B., & Feldmann, H. (2014). Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques. Proceedings of the National Academy of Sciences of the United States of America, 111(19), 7114-7119. https://doi.org/10.1073/pnas.1401998111