Simian hemorrhagic fever virus infection of rhesus macaques as a model of viral hemorrhagic fever: clinical characterization and risk factors for severe disease.
Simian Hemorrhagic Fever Virus (SHFV) has caused sporadic outbreaks of hemorrhagic fevers in macaques at primate research facilities. SHFV is a BSL-2 pathogen that has not been linked to human disease; as such, investigation of SHFV pathogenesis in non-human primates (NHPs) could serve as a model for hemorrhagic fever viruses such as Ebola, Marburg, and Lassa viruses. Here we describe the pathogenesis of SHFV in rhesus macaques inoculated with doses ranging from 50 PFU to 500,000 PFU. Disease severity was independent of dose with an overall mortality rate of 64% with signs of hemorrhagic fever and multiple organ system involvement. Analyses comparing survivors and non-survivors were performed to identify factors associated with survival revealing differences in the kinetics of viremia, immunosuppression, and regulation of hemostasis. Notable similarities between the pathogenesis of SHFV in NHPs and hemorrhagic fever viruses in humans suggest that SHFV may serve as a suitable model of BSL-4 pathogens.
Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. johnsonreed@mail.nih.gov
Reed F
RF
Johnson
Lori E
LE
Dodd
Srikanth
S
Yellayi
Wenjuan
W
Gu
Jennifer A
JA
Cann
Catherine
C
Jett
John G
JG
Bernbaum
Dan R
DR
Ragland
Marisa
M
St Claire
Russell
R
Byrum
Jason
J
Paragas
Joseph E
JE
Blaney
Peter B
PB
Jahrling
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D018018:Arterivirus / Q000276:immunology / Q000472:pathogenicity; D018174:Arterivirus Infections / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000821:virology; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D006482:Hemorrhagic Fevers, Viral / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000821:virology; D007108:Immune Tolerance; D008253:Macaca mulatta; D012307:Risk Factors
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D018925:Chemokines; D016207:Cytokines