Reactive oxygen species-related oxidative changes are associated with splenic lymphocyte depletion in Ebola virus infection.

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.