In a study published today in the Open Access journal PLOS Pathogens, researchers at Emory University have discovered a potentially important mechanism by which the Ebola virus alters and evades the immune response of its infected host.
Ebola virus is the causative agent of Ebola Hemorrhagic Fever (EHF), a disease with up to 90 percent mortality. While human outbreaks of Ebola hemorrhagic fever have been confined to Africa, Ebola virus infections in bats, the presumed natural reservoir of the virus, have also been detected in Europe and Asia.
The high lethality of the disease, combined with its short incubation period and the lack of vaccines or effective treatments, makes Ebola virus a significant public health threat as well as a potentially devastating biological weapon. Efforts to develop a vaccine against Ebola virus have been met with limited success, and it is likely that the virus employs complex immune evasion mechanisms that present unique challenges for vaccine design. Understanding these evasion mechanisms is a critical first step in developing an effective vaccine.
In this study, the authors examined the role of a protein secreted in large quantities by Ebola virus-infected cells. The protein shares regions with a membrane protein that the virus expresses on its surface and uses to initiate the infection process. The authors studied antibodies generated by immunizing mice with the viral surface protein and/or the secreted protein. They determined that the secreted protein can selectively drive induction of antibody responses to itself and also compete for antibodies to the viral surface protein that would otherwise bind to and inactivate the virus.
"Our findings provide an explanation for the lack of protective antibodies against the viral surface protein in patients who have survived Ebola virus infection," says Dr. Chinglai Yang, assistant professor of microbiology and immunology at the Emory University School of Medicine. "We hypothesize that the secreted protein allows the virus to subvert the host antibody response in vivo, and that this may enable the virus to cause repeated or sustained infection in its natural reservoir."
The results suggest that immunity induced by a vaccine may need to reach a sufficient threshold to effectively neutralize the incoming virus to protect against Ebola virus infection. These findings raise new challenges for Ebola vaccine design, as vaccines will most likely have to be tailored to overcome or avoid the ability of the secreted decoy protein to interfere with host immune responses. Such approaches could enable the development of more efficacious vaccines to prevent Ebola virus infection.
FINANCIAL DISCLOSURE: This study is supported by Public Health Service grants 1R01AI093406 and 1R01AI069148 from the National Institute of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
COMPETING INTERESTS: The authors have declared that no competing interests exist.
PLEASE ADD THIS LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.plos.org/10.1371/journal.ppat.1003065 (link will go live upon embargo lift)
CITATION: Mohan GS, Li W, Ye L, Compans RW, Yang C (2012) Antigenic Subversion: A Novel Mechanism of Host Immune Evasion by Ebola Virus. PLoS Pathog 8(12): e1003065. doi:10.1371/journal.ppat.1003065
Institutional Media Contact:
PLOS Media Contact:
This press release refers to an upcoming article in PLOS Pathogens. The release is provided by the article authors. Any opinions expressed in these releases or articles are the personal views of the journal staff and/or article contributors, and do not necessarily represent the views or policies of PLOS. PLOS expressly disclaims any and all warranties and liability in connection with the information found in the releases and articles and your use of such information.
PLOS Journals publish under a Creative Commons Attribution License, which permits free reuse of all materials published with the article, so long as the work is cited (e.g., Kaltenbach LS et al. (2007) Huntingtin Interacting Proteins Are Genetic Modifiers of Neurodegeneration. PLoS Genet 3(5): e82. doi:10.1371/journal.pgen.0030082). No prior permission is required from the authors or publisher. For queries about the license, please contact the relative journal contact indicated here: http://www.plos.org/about/media-inquiries/.
About PLOS Pathogens
PLOS Pathogens publishes outstanding original articles that significantly advance the understanding of pathogens and how they interact with their host organisms. All works published in PLOS Pathogens are open access. Everything is immediately available subject only to the condition that the original authorship and source are properly attributed. Copyright is retained by the authors. The Public Library of Science uses the Creative Commons Attribution License.
About the Public Library of Science
The Public Library of Science (PLOS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit http://www.plos.org.
AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.