Ebola Virus Disease Features Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome in the Rhesus Macaque Model

J Infect Dis. 2023 Aug 16;228(4):371-382. doi: 10.1093/infdis/jiad203.


Background: Ebola virus (EBOV) disease (EVD) is one of the most severe and fatal viral hemorrhagic fevers and appears to mimic many clinical and laboratory manifestations of hemophagocytic lymphohistiocytosis syndrome (HLS), also known as macrophage activation syndrome. However, a clear association is yet to be firmly established for effective host-targeted, immunomodulatory therapeutic approaches to improve outcomes in patients with severe EVD.

Methods: Twenty-four rhesus monkeys were exposed intramuscularly to the EBOV Kikwit isolate and euthanized at prescheduled time points or when they reached the end-stage disease criteria. Three additional monkeys were mock-exposed and used as uninfected controls.

Results: EBOV-exposed monkeys presented with clinicopathologic features of HLS, including fever, multiple organomegaly, pancytopenia, hemophagocytosis, hyperfibrinogenemia with disseminated intravascular coagulation, hypertriglyceridemia, hypercytokinemia, increased concentrations of soluble CD163 and CD25 in serum, and the loss of activated natural killer cells.

Conclusions: Our data suggest that EVD in the rhesus macaque model mimics pathophysiologic features of HLS/macrophage activation syndrome. Hence, regulating inflammation and immune function might provide an effective treatment for controlling the pathogenesis of acute EVD.

Keywords: Ebola virus disease; hemophagocytic lymphohistiocytosis syndrome; macrophage activation syndrome; sCD163; sCD25.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Ebolavirus*
  • Hemorrhagic Fever, Ebola*
  • Lymphohistiocytosis, Hemophagocytic*
  • Macaca mulatta
  • Macrophage Activation Syndrome* / therapy