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Journal of Virology, September 2007, p. 9536-9545, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.02636-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Phase-Dependent Immune Evasion of Herpesviruses ^,

Tal Vider-Shalit, Vered Fishbain, Shai Raffaeli, and Yoram Louzoun^*

Math Department, Bar Ilan University, Ramat Gan, Israel

Received 29 November 2006/ Accepted 22 June 2007

Viruses employ various modes to evade immune detection. Two possible evasion modes are a reduction of the number of epitopes presented and the mimicry of host epitopes. The immune evasion efforts are not uniform among viral proteins. The number of epitopes in a given viral protein and the similarity of the epitopes to host peptides can be used as a measure of the viral attempts to hide this protein. Using bioinformatics tools, we here present a genomic analysis of the attempts of four human herpesviruses (herpes simplex virus type 1-human herpesvirus 1, Epstein-Barr virus-human herpesvirus 4, human cytomegalovirus-human herpesvirus 5, and Kaposi's sarcoma-associated herpesvirus-human herpesvirus 8) and one murine herpesvirus (murine herpesvirus 68) to escape from immune detection. We determined the full repertoire of CD8 T-lymphocyte epitopes presented by each viral protein and show that herpesvirus proteins present many fewer epitopes than expected. Furthermore, the epitopes that are presented are more similar to host epitopes than are random viral epitopes, minimizing the immune response. We defined a score for the size of the immune repertoire (the SIR score) based on the number of epitopes in a protein. The numbers of epitopes in proteins expressed in the latent and early phases of infection were significantly smaller than those in proteins expressed in the lytic phase in all tested viruses. The latent and immediate-early epitopes were also more similar to host epitopes than were lytic epitopes. A clear trend emerged from the analysis. In general, herpesviruses demonstrated an effort to evade immune detection. However, within a given herpesvirus, proteins expressed in phases critical to the fate of infection (e.g., early lytic and latent) evaded immune detection more than all others. The application of the SIR score to specific proteins allows us to quantify the importance of immune evasion and to detect optimal targets for immunotherapy and vaccine development.

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* Corresponding author. Mailing address: Math Department, Bar Ilan University, Ramat Gan, Israel. Phone: 972-3-5317610. Fax: 972-3-7384057. E-mail: louzouy{at}math.biu.ac.il

Published ahead of print on 3 July 2007.

Supplemental material for this article may be found at http://jvi.asm.org/.

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Journal of Virology, September 2007, p. 9536-9545, Vol. 81, No. 17
0022-538X/07/$08.00+0     doi:10.1128/JVI.02636-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Vider-Shalit, T., Sarid, R., Maman, K., Tsaban, L., Levi, R., Louzoun, Y. (2009). Viruses selectively mutate their CD8+ T-cell epitopes--a large-scale immunomic analysis. Bioinformatics 25: i39-i44 [Abstract] [Full Text]