Pathogenesis of Rift Valley fever in rhesus monkeys: role of interferon response.
Rhesus monkeys inoculated intravenously with Rift Valley fever (RVF) virus presented clinical disease syndromes similar to human cases of RVF. All 17 infected monkeys had high-titered viremias but disease ranged from clinically inapparent to death. Three (18%) RVF virus-infected monkeys developed signs of hemorrhagic fever characterized by epistaxis, petechial to purpuric cutaneous lesions, anorexia, and vomiting prior to death. The 14 remaining monkeys survived RVF viral infection but, 7 showed clinical signs of illness characterized by diminished food intake, cutaneous petechiae, and occasional vomiting. The other 7 monkeys showed no evidence of clinical disease. All monkeys had detectable serum interferon 24-30 h after infection, but 4 of 7 monkeys that did not develop clinical illness had serum interferon titers within 12 h after infection. In lethally infected macaques, indices of hepatic function and blood coagulation were abnormal within 2 days, implicating early pathogenetic events as critical determinants of survival. Serum transferase values were elevated in proportion to severity of clinical disease and outcome of infection. Both myocardial damage and laboratory evidence consistent with disseminated intravascular coagulation were present in fatal infections. All surviving monkeys developed neutralizing antibodies to RVF virus 4-7 days after infection, and this coincided with termination of viremia. Two fatally infected monkeys were viremic until death on days 6 and 8, and the third cleared viremia on day 5 and developed antibody on day 6 but died on day 15. There was a significant correlation between a delayed interferon response and mortality, suggesting that the early appearance of interferon was influential in limiting the severity of disease.
Disease Assessment, Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland.
J C
JC
Morrill
G B
GB
Jennings
A J
AJ
Johnson
T M
TM
Cosgriff
P H
PH
Gibbs
C J
CJ
Peters
D000704:Analysis of Variance; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000502:physiology; D005260:Female; D006403:Hematologic Tests; D007372:Interferons / Q000097:blood / Q000502:physiology*; D008253:Macaca mulatta; D008297:Male; D009500:Neutralization Tests; D012295:Rift Valley Fever / Q000097:blood / Q000276:immunology* / Q000473:pathology; D012296:Rift Valley fever virus / Q000302:isolation & purification / Q000472:pathogenicity; D013997:Time Factors; D014766:Viremia / Q000209:etiology / Q000276:immunology
D000914:Antibodies, Viral; D007372:Interferons