Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques.
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.
Laboratory of Virology.
David
D
Safronetz
Laboratory of Virology.
Joseph
J
Prescott
Rocky Mountain Veterinary Branch, and.
Friederike
F
Feldmann
Laboratory of Virology.
Elaine
E
Haddock
Rocky Mountain Veterinary Branch, and.
Rebecca
R
Rosenke
Department of Microbiology, University of Washington, Seattle, WA 98195;
Atsushi
A
Okumura
Rocky Mountain Veterinary Branch, and.
Douglas
D
Brining
Genomics Unit, Rocky Mountain Laboratory Research Technologies Section, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840;
Eric
E
Dahlstrom
Genomics Unit, Rocky Mountain Laboratory Research Technologies Section, Rocky Mountain Laboratories, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840;
Stephen F
SF
Porcella
Laboratory of Virology.
Hideki
H
Ebihara
Rocky Mountain Veterinary Branch, and.
Dana P
DP
Scott
Center for Infectious Diseases and Immunity, Department of Pathology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131; and.
Brian
B
Hjelle
Laboratory of Virology,Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada R3E 0J9 feldmannh@niaid.nih.gov.
Heinz
H
Feldmann
D000818:Animals; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D018804:Hantavirus Pulmonary Syndrome / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000635:transmission; D008168:Lung / Q000000981:diagnostic imaging / Q000821:virology; D008253:Macaca mulatta / Q000821:virology*; D008969:Molecular Sequence Data; D008992:Monkey Diseases / Q000503:physiopathology / Q000635:transmission / Q000821:virology*; D009656:North America; D010542:Peromyscus / Q000821:virology*; D012367:RNA, Viral / Q000235:genetics; D011859:Radiography; D029261:Sin Nombre virus / Q000235:genetics*; D014709:Vero Cells; D014766:Viremia / Q000503:physiopathology
D012367:RNA, Viral
New World hantaviruses; disease modeling; emerging pathogen