Een interdisciplinaire studie waarbij we de rol van HLA genen en T-cel diversiteit als risicofactoren voor herpes zoster bestuderen.

Een interdisciplinaire studie waarbij we de rol van HLA genen en T-cel diversiteit als risicofactoren voor herpes zoster bestuderen.Chickenpox is a consequence of primary infection of varicella-zoster virus (VZV). Afterwards, VZV remains latent in neural ganglia until symptomatic reactivation called herpes zoster (HZ, shingles). In this project, we will first develop a novel computational framework that will allow us to estimate the probability that a pathogen-derived antigen is adequately recognised by the major histocompatibility complexes (MHC) encoded by HLA genes. Antigen bounding by MHC molecules is a necessary step prior to recognition (and further management) of infected cells. Next, we will obtain HLA data from 150 HZ patients and 150 matched controls. This will allow us to estimate whether and which HLA A/B/C genes are enriched or depleted in HZ patients. Our computational framework will allow us to estimate which VZV proteins are most likely of importance in controlling VZV. We will assess whether the HLA data is readily translated into the diversity of the T-cell receptor (TCR) against VZV, and against which of the most important VZV proteins. Finally, we will differentiate blood-derived inducible pluripotent stem cells (iPSC) into neuronal cells, infect these neuronal cells with VZV and study whether depletion of VZV-specific T-cells affects VZV proliferation, thereby confirming our earlier obtained HLA-TCR predictions.

Trefwoorden:HERPES ZOSTER

Disciplines:Scientific computing, Bio-informatica en computationele biologie, Genetica, Systeembiologie, Moleculaire en celbiologie, Maatschappelijke gezondheidszorg, Publieke medische diensten