Human Ebola virus infection results in substantial immune activation

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

Research output: Contribution to journalArticlepeer-review

160 Scopus citations

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.

Original languageEnglish
Pages (from-to)4719-4724
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number15
DOIs
StatePublished - Apr 14 2015
Externally publishedYes

Keywords

  • Ebola infection
  • Human immune response
  • Immune activation
  • Plasmablasts
  • T cells

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