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Author Notes:

Email Address: Christina F. Spiropoulou :ccs8@cdc.gov Rafi Ahmed :rahmed@emory.edu

A.K. Mehta, C.S.K., G.M.L., B.S.R., J.V., U.S., I.D., S.T.N., C.F.S., and R.A. designed research; A.K. McElroy and S.C. performed research;

A.K. Mehta led the clinical team; C.S.K., G.M.L., B.S.R., and J.V. composed the clinical team; J.S. and A.S. contributed new reagents/analytic tools;

R.S.A., C.W.D., A.H.E., A.S., and R.A. analyzed data; and A.K. McElroy, R.S.A., and R.A. wrote the paper

We are most grateful to the patients for participating in the study, and thank the Emory Serious Communicable Diseases Unit team for their assistance.

We thank Tim Uyeki for providing coordination between the clinical and research staff, and Tatyana Klimova for help with the manuscript.

The authors declare no conflict of interest.

Subjects:

Research Funding:

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:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • Ebola infection
  • human immune response
  • immune activation
  • plasmablasts
  • T cells
  • T-CELL RESPONSES
  • HEMORRHAGIC-FEVER
  • LYMPHOCYTE APOPTOSIS
  • NONHUMAN-PRIMATES
  • DENDRITIC CELLS
  • MARBURG VIRUSES
  • IN-VITRO
  • CHALLENGE
  • VACCINES
  • KIKWIT

Human Ebola virus infection results in substantial immune activation

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Journal Title:

Proceedings of the National Academy of Sciences

Volume:

Volume 112, Number 15

Publisher:

, Pages 4719-4724

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

Freely available online through the PNAS open access option.

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