Abstract
The varicella zoster virus (VZV) causes the childhood disease commonly known as chickenpox and can later in life reactivate as herpes zoster. The adaptive immune system is known to play an important role in suppressing VZV reactivation. A central aspect of this system is the presentation of VZV-derived peptides by the major histocompatibility complex (MHC) proteins. Here, we investigate if key VZV proteins have evolved their amino acid sequence to avoid presentation by MHC based on predictive models of MHC-peptide affinity. This study shows that the immediate-early proteins of all characterized VZV strains are profoundly depleted for high-affinity MHC-I-restricted epitopes. The same depletion can be found in its closest animal analog, the simian varicella virus. Further orthology analysis towards other herpes viruses suggests that the protein amino acid frequency is one of the primary drivers of targeted epitope depletion.
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Acknowledgments
This work was supported by the Fund for Scientific Research—Flanders (FWO-Vlaanderen; personal grant to B.O., and project grants G.0409.12N and G.0903.13N) and the University of Antwerp Concerted Research Action 30730 and Small Project 31034.
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Online Resource 1
High affinity peptide counts for VZV Dumas strain.xls. A raw data table containing the high affinity peptide counts for each VZV Dumas ORF and each HLA allele as analyzed in this study. Furthermore it contains the uncorrected and corrected P values for epitope depletion for each combination. (XLS 170 kb)
Online Resource 2
Analysis of epitope counts for VZV Dumas.pdf. A detailed analysis on the high affinity counts for VZV Dumas with respect to their distribution among VZV genes for HLA-A*02:01. It contains figure S2.1, which shows the strong relationship between high affinity peptide count per ORF and ORF length, and figure S2.2, which shows the difference in high affinity peptides counts for the different VZV ORFs. (PDF 80.3 kb)
Online Resource 3
Peptide depletion for mouse MHC variants.pdf. A repeat of the VZV depletion analysis described in the main manuscript but for common mouse MHC variants instead of human MHC variants. Figure S3.1 shows a similar depletion pattern to Figure 1 for these mouse MHC variants. (PDF 62.9 kb)
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Meysman, P., Fedorov, D., Van Tendeloo, V. et al. Immunological evasion of immediate-early varicella zoster virus proteins. Immunogenetics 68, 483–486 (2016). https://doi.org/10.1007/s00251-016-0911-4
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DOI: https://doi.org/10.1007/s00251-016-0911-4