Human Ebola virus infection results in substantial immune activation

• Type of Material: Article
• Authors: Anita McElroy, Emory University; Rama Akondy, Emory University; Carl Davis, Emory University; Ali H. Ellebedy, Emory University; Aneesh K Mehta, Emory University; Colleen S Kraft, Emory University; G Marshall Lyon III, Emory University; Bruce Ribner, Emory University; Jay Varkey, Emory University; John Sidney, La Jolla Institute for Allergy and Immunology; Alessandro Sette, La Jolla Institute for Allergy and Immunology; Shelley Campbell, Centers for Disease Control and Prevention; Ute Stroher, Centers for Disease Control and Prevention; Inger Damon, Centers for Disease Control and Prevention; Stuart Nichol, Emory University; Christina F. Spiropoulou, Centers for Disease Control and Prevention; Rafi Ahmed, Emory University
• Language: English
• Date: 2015-04-14
• Publisher: National Academy of Sciences
• Publication Version: Final Published Version
• Copyright Statement: Freely available online through the PNAS open access option.
• Final Published Version (URL): http://dx.doi.org/10.1073/pnas.1502619112
• Title of Journal or Parent Work: Proceedings of the National Academy of Sciences
• ISSN: 1091-6490
• Volume: 112
• Issue: 15
• Start Page: 4719
• End Page: 4724
• Grant/Funding Information: This project is supported by funding from the Defense Advanced Research Projects Agency (W31P4Q-14-1-0010) and NIH (UL1TR000454).; A.K. McElroy is supported by a Pediatric Infectious Disease Society/St. Jude’s Fellowship Award, a Burroughs Wellcome Career Award, and NIH K12 HD072245.
• Keywords: KIKWIT; Science & Technology; IN-VITRO; DENDRITIC CELLS; Ebola infection; CHALLENGE; human immune response; plasmablasts; T cells; T-CELL RESPONSES; VACCINES; Multidisciplinary Sciences; immune activation; HEMORRHAGIC-FEVER; LYMPHOCYTE APOPTOSIS; Science & Technology - Other Topics; MARBURG VIRUSES; NONHUMAN-PRIMATES
• Research Categories: Health Sciences, General; Health Sciences, Immunology; Biology, Virology

Abstract

Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.