Abstract
Around 30% of individuals will develop herpes zoster (HZ), caused by the varicella zoster virus (VZV), during their life. While several risk factors for HZ, such as immunosuppressive therapy, are well known, the genetic and molecular components that determine the risk of otherwise healthy individuals to develop HZ are still poorly understood. We created a computational model for the Human Leukocyte Antigen (HLA-A, -B, and -C) presentation capacity of peptides derived from the VZV Immediate Early 62 (IE62) protein. This model could then be applied to a HZ cohort with known HLA molecules. We found that HLA-A molecules with poor VZV IE62 presentation capabilities were more common in a cohort of 50 individuals with a history of HZ compared to a nationwide control group, which equated to a HZ risk increase of 60%. This tendency was most pronounced for cases of HZ at a young age, where other risk factors are less prevalent. These findings provide new molecular insights into the development of HZ and reveal a genetic predisposition in those individuals most at risk to develop HZ.
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Acknowledgements
The authors would like to thank all participants and recruiters for their participation. This work was supported by the University of Antwerp [BOF Concerted Research Action, BOF Small Project 31034, predoctoral fellowship to JVDB, Antwerp Study Center for Infectious Diseases, Methusalem funding] and the Research Foundation Flanders (FWO) [Personal grants to NDN and BO; project grant G.0409.12 N and G.0903.13 N; the Hercules Foundation—Belgium].
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Meysman, P., De Neuter, N., Bartholomeus, E. et al. Increased herpes zoster risk associated with poor HLA-A immediate early 62 protein (IE62) affinity. Immunogenetics 70, 363–372 (2018). https://doi.org/10.1007/s00251-017-1047-x
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DOI: https://doi.org/10.1007/s00251-017-1047-x