Reactive oxygen species-related oxidative changes are associated with splenic lymphocyte depletion in Ebola virus infection
Venkatesh Mani,
Winston T. Chu,
Hee-Jeong Yang,
C. Paul Morris,
Joseph Laux,
Russell Byrum,
Kurt Cooper,
David X. Liu,
Hui Wang,
Cristal Johnson,
Kyra Hadley,
John G. Bernbaum,
Randy Hart,
Scott M. Anthony,
Anthony E. Marketon,
Rebecca Bernbaum-Cutler,
Bapi Pahar,
Gabriella Worwa,
Jens H. Kuhn,
Ian Crozier,
Claudia Calcagno,
Eric Gale
Affiliations
Venkatesh Mani
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
Winston T. Chu
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
Hee-Jeong Yang
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
C. Paul Morris
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
Joseph Laux
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
Russell Byrum
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
Kurt Cooper
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
David X. Liu
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
Hui Wang
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
Cristal Johnson
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
Kyra Hadley
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
John G. Bernbaum
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
Randy Hart
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
Scott M. Anthony
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
Anthony E. Marketon
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
Rebecca Bernbaum-Cutler
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
Bapi Pahar
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
Gabriella Worwa
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
Jens H. Kuhn
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
Ian Crozier
Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research
Claudia Calcagno
Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick
Eric Gale
Athinoula A. Martinos Center for Biomedical Imaging, The Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital
Abstract The dysregulated production of reactive oxygen species (ROS) during viral infections may lead to immune cell death and ineffective host responses. ROS dynamics have been under-investigated in severe Ebola virus disease (EVD), a condition in which hyperinflammation and excessive immune cell death are well described but poorly understood. Through ex vivo immunohistochemistry and in vivo ROS-sensitive magnetic resonance imaging (MRI) we demonstrate significant ROS-related oxidative changes in the spleens of domestic ferrets exposed to Ebola virus (EBOV). By immunohistochemistry or MRI, detection of splenic ROS was inversely correlated with the number of CD4+/CD8+ T lymphocytes and apoptotic CD8+ lymphocytes, but detection was positively correlated with the frequency of apoptotic CD4+ cells and the number and frequency of apoptotic B lymphocytes. These results suggest that ROS-induced apoptosis may contribute to the loss of splenic CD4+ T lymphocytes in EBOV-exposed ferrets and warrant further investigation of the role of ROS in severe EVD.
