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Author Notes:

Author Correspondence: rcompan@emory.edu (RWC); chyang@emory.edu (CY)

Conceived and designed the experiments: CY LY RWC.

Performed the experiments: GSM WL.

Analyzed the data: GSM LY CY RWC.

Wrote the paper: GSM CY RWC.

The authors acknowledge Thuc Vy Le, Neil Haig, and Lei Pan for technical assistance and Brantley Herrin, Thuc Vy Le, Daniel Claiborne, and Neil Haig for helpful discussion

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Subjects:

Research Funding:

This study is supported by Public Health Service grants 1R01AI093406 and 1R01AI069148 from the National Institute of Health.

Antigenic Subversion: A Novel Mechanism of Host Immune Evasion by Ebola Virus

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Journal Title:

PLoS Pathogens

Volume:

Volume 8, Number 12

Publisher:

, Pages e1003065-e1003065

Type of Work:

Article | Final Publisher PDF

Abstract:

In addition to its surface glycoprotein (GP1,2), Ebola virus (EBOV) directs the production of large quantities of a truncated glycoprotein isoform (sGP) that is secreted into the extracellular space. The generation of secreted antigens has been studied in several viruses and suggested as a mechanism of host immune evasion through absorption of antibodies and interference with antibody-mediated clearance. However such a role has not been conclusively determined for the Ebola virus sGP. In this study, we immunized mice with DNA constructs expressing GP1,2 and/or sGP, and demonstrate that sGP can efficiently compete for anti-GP12 antibodies, but only from mice that have been immunized by sGP. We term this phenomenon “antigenic subversion”, and propose a model whereby sGP redirects the host antibody response to focus on epitopes which it shares with membrane-bound GP1,2, thereby allowing it to absorb anti-GP1,2 antibodies. Unexpectedly, we found that sGP can also subvert a previously immunized host's anti-GP1,2 response resulting in strong cross-reactivity with sGP. This finding is particularly relevant to EBOV vaccinology since it underscores the importance of eliciting robust immunity that is sufficient to rapidly clear an infection before antigenic subversion can occur. Antigenic subversion represents a novel virus escape strategy that likely helps EBOV evade host immunity, and may represent an important obstacle to EBOV vaccine design.

Copyright information:

© 2012 Mohan et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 2.5 Generic License (http://creativecommons.org/licenses/by/2.5/).

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