Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2015 Apr 14;112(15):4719-24. doi: 10.1073/pnas.1502619112. Epub 2015 Mar 9.

Human Ebola virus infection results in substantial immune activation.

Author information

1
Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333; Division of Pediatric Infectious Disease.
2
Emory Vaccine Center, Department of Microbiology and Immunology.
3
Division of Infectious Diseases, and.
4
Division of Infectious Diseases, and Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322; and.
5
La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
6
Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333;
7
Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA 30333; ccs8@cdc.gov rahmed@emory.edu.
8
Emory Vaccine Center, Department of Microbiology and Immunology, ccs8@cdc.gov rahmed@emory.edu.

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.

KEYWORDS:

Ebola infection; T cells; human immune response; immune activation; plasmablasts

PMID:
25775592
PMCID:
PMC4403189
DOI:
10.1073/pnas.1502619112
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center