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

Author:

Liu, David X [ORCID]

Pahar, Bapi

Cooper, Timothy K

Perry, Donna L

Xu, Huanbin

Huzella, Louis M

Adams, Ricky D

Hischak, Amanda M W

Hart, Randy J

Bernbaum, Rebecca

Rivera, Deja

Anthony, Scott

St Claire, Marisa

Byrum, Russell

Cooper, Kurt

Reeder, Rebecca

Kurtz, Jonathan

Hadley, Kyra

Wada, Jiro

Crozier,Ian

Worwa, Gabriella

Bennett, Richard S

Warren, Travis

Holbrook, Michael R [ORCID]

Schmaljohn, Connie S

Hensley, Lisa E
Author Address

Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA., Department of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, USA., Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.,

Abstract:

Ebola virus 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 (MAS). 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. Twenty-four rhesus monkeys were exposed intramuscularly to the Ebola virus (EBOV) Kikwit 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. EBOV-exposed monkeys presented with clinicopathologic features of HLS, including fever, multi-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. Our data suggest that EVD in the rhesus macaque model mimics pathophysiologic features of HLS/MAS. Hence, regulating inflammation and immune function might provide an effective treatment for controlling acute EVD pathogenesis. Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.

See More

Author Address