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Unraveling the immune signature of herpes zoster: Insights into pathophysiology and the HLA risk profile

Vandoren, R.; Boeren, M.; Shippers, J.; Bartholomeus, E.; Michels, N.; Aerts, O.; Leysen, J.; Bervoets, A.; Lambert, J.; Leuridan, E.; Wens, J.; Peeters, K.; Jansens, H.; Suls, A.; Van Tendeloo, V.; Ponsaerts, P.; Delputte, P.; Ogunjimi, B.; Meysman, P.; Laukens, K.

2023-02-26 infectious diseases
10.1101/2023.02.24.23286421 medRxiv
Show abstract

The varicella-zoster virus (VZV) infects over 95% of the population and establishes latency afterwards. Reactivation of VZV causes herpes zoster (HZ), commonly known as shingles, which presents as a painful rash in mostly the elderly and people with a weakened immune system. However, HZ might occur in otherwise healthy individuals too. In this study, we have studied the immune signature of HZ to better understand HZs pathophysiology. We provide a general overview of the antiviral state and the activation of innate and adaptive immune responses during HZ. Differential gene expression and gene ontology analyses revealed upregulation of several genes and host immune pathways during herpes zoster, especially related to type I IFN response but also related to adaptive immune responses. Intriguingly, no differences in gene expression were noted during convalescence between HZ patients and controls. Furthermore, we conducted the largest HLA association study on HZ to date using the UK Biobank and identified seven protective and four risk HLA alleles associated with the development of herpes zoster. These findings reveal key genes and pathways involved in the host immune response to symptomatic VZV reactivation and provide new molecular insights into the development of HZ.

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