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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/18304

Title: Varicella-Zoster Virus-Derived Major Histocompatibility Complex Class I-Restricted Peptide Affinity Is a Determining Factor in the HLA Risk Profile for the Development of Postherpetic Neuralgia
Authors: Meysman, Pieter
OGUNJIMI, Benson
Naulaerts, Stefan
Beutels, Philippe
Van Tendeloo, Viggo
Laukens, Kris
Issue Date: 2015
Publisher: AMER SOC MICROBIOLOGY
Citation: JOURNAL OF VIROLOGY, 89 (2), p. 962-969
Abstract: Postherpetic neuralgia (PHN) is the most common complication of herpes zoster and is typified by a lingering pain that can last months or years after the characteristic herpes zoster rash disappears. It is well known that there are risk factors for the development of PHN, such as its association with certain HLA alleles. In this study, previous HLA genotyping results were collected and subjected to a meta-analysis with increased statistical power. This work shows that the alleles HLA-A*33 and HLA-B*44 are significantly enriched in PHN patients, while HLA-A*02 and HLA-B*40 are significantly depleted. Prediction of the varicella-zoster virus (VZV) peptide affinity for these four HLA variants by using one in-house-developed and two existing state-of-the-art major histocompatibility complex (MHC) class I ligand prediction methods reveals that there is a great difference in their absolute and relative peptide binding repertoires. It was observed that HLA-A*02 displays a high affinity for an similar to 7-fold-higher number of VZV peptides than HLA-B*44. Furthermore, after correction for HLA allele-specific limitations, the relative affinity of HLA-A*33 and HLA-B*44 for VZV peptides was found to be significantly lower than those of HLA-A*02 and HLA-B*40. In addition, HLA peptide affinity calculations indicate strong trends for VZV to avoid high-affinity peptides in some of its proteins, independent of the studied HLA allele. IMPORTANCE Varicella-zoster virus can cause two distinct diseases: chickenpox (varicella) and shingles (herpes zoster). Varicella is a common disease in young children, while herpes zoster is more frequent in older individuals. A common complication of herpes zoster is postherpetic neuralgia, a persistent and debilitating pain that can remain months up to years after the resolution of the rash. In this study, we show that the relative affinity of HLA variants associated with higher postherpetic neuralgia risk for varicella-zoster virus peptides is lower than that of variants with a lower risk. These results provide new insight into the development of postherpetic neuralgia and strongly support the hypothesis that one of its possible underlying causes is a suboptimal anti-VZV immune response due to weak HLA binding peptide affinity.
Notes: [Meysman, Pieter; Naulaerts, Stefan; Laukens, Kris] Univ Antwerp, Dept Math & Comp Sci, B-2020 Antwerp, Belgium. [Meysman, Pieter; Naulaerts, Stefan; Laukens, Kris] Univ Antwerp, Univ Antwerp Hosp, Biomed Informat Res Ctr Antwerp Biomina, Edegem, Belgium. [Ogunjimi, Benson; Beutels, Philippe] Univ Antwerp, Ctr Hlth Econ Res & Modeling Infect Dis, Vaccine Infect Dis Inst VAXINFECTIO, B-2020 Antwerp, Belgium. [Ogunjimi, Benson; Van Tendeloo, Viggo] Univ Antwerp, Lab Expt Hematol, Vaccine & Infect Dis Inst VAXINFECTIO, B-2020 Antwerp, Belgium. [Ogunjimi, Benson] Hasselt Univ, Interuniv Inst Biostat & Stat Bioinformat, Hasselt, Belgium.
URI: http://hdl.handle.net/1942/18304
DOI: 10.1128/JVI02500-14
ISI #: 000347178900007
ISSN: 0022-538X
Category: A1
Type: Journal Contribution
Validation: ecoom, 2016
Appears in Collections: Research publications

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