Human Ebola virus infection results in substantial immune activation.

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.

• Authors: Anita K McElroy, Rama S Akondy, Carl W Davis, Ali H Ellebedy, Aneesh K Mehta, Colleen S Kraft, G Marshall Lyon, Bruce S Ribner, Jay Varkey, John Sidney, Alessandro Sette, Shelley Campbell, Ute Ströher, Inger Damon, Stuart T Nichol, Christina F Spiropoulou, Rafi Ahmed
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 112 Issue 15 Pg. 4719-24 (Apr 14 2015) ISSN: 1091-6490 [Electronic] United States
• PMID: 25775592 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Immunoglobulin G
• Tumor Necrosis Factor-alpha
• Viral Proteins
• Interferon-gamma

Topics

• CD4-Positive T-Lymphocytes (immunology, metabolism)
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Ebolavirus (immunology, metabolism)
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Hemorrhagic Fever, Ebola (blood, immunology, virology)
• Humans
• Immunity, Cellular (immunology)
• Immunity, Humoral (immunology)
• Immunoglobulin G (blood, immunology)
• Immunophenotyping
• Interferon-gamma (immunology, metabolism)
• Lymphocyte Activation (immunology)
• Precursor Cells, B-Lymphoid (immunology, metabolism)
• Tumor Necrosis Factor-alpha (immunology, metabolism)
• Viral Proteins (immunology, metabolism)