title: Dengue virus-induced hemorrhage in a nonhuman primate model.
abstract: Lack of a dengue hemorrhagic animal model recapitulating human dengue virus infection has been a significant impediment in advancing our understanding of the early events involved in the pathogenesis of dengue disease. In efforts to address this issue, a group of rhesus macaques were intravenously infected with dengue virus serotype 2 (strain 16 681) at 1 x 10(7) PFU/animal. A classic dengue hemorrhage developed 3 to 5 days after infection in 6 of 6 animals. Blood chemistry appeared to be normal with exception of creatine phosphokinase, which peaked at 7 days after infection. A modest thrombocytopenia and noticeable neutropenia concomitant with slight decrease of hemoglobin and hematocrit were registered. In addition, the concentration of D-dimer was elevated significantly. Viremia peaked at 3 to 5 days after infection followed by an inverse relationship between T and B lymphocytes and a bimodal pattern for platelet-monocytes and platelet-neutrophil aggregates. Dengue virus containing platelets engulfed by monocytes was noted at 8 or 9 days after infection. Thus, rhesus macaques inoculated intravenously with a high dose of dengue virus produced dengue hemorrhage, which may provide a unique platform to define the early events in dengue virus infection and help identify which blood components contribute to the pathogenesis of dengue disease.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: Nattawat
authors.initials: N
authors.lastname: Onlamoon
authors.forename: Sansanee
authors.initials: S
authors.lastname: Noisakran
authors.forename: Hui-Mien
authors.initials: HM
authors.lastname: Hsiao
authors.forename: Alexander
authors.initials: A
authors.lastname: Duncan
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
authors.forename: Guey Chuen
authors.initials: GC
authors.lastname: Perng
mesh_terms: D000818:Animals; D003716:Dengue Virus / Q000472:pathogenicity; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D010974:Platelet Aggregation; D019595:Severe Dengue / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000821:virology; D013997:Time Factors; D019562:Viral Load