We are a team of clinicians and basic researchers combining a wide range of scientific and technological expertise in the fields of virology, pathogenesis, neurology, dermatology and epigenetics, facilitating the success of the project.
We look into the proposed challenges from the perspective of the virus and the human being. VZV is a human specific virus that establishes latency and reactivates in neurons. Therefore, to investigate VZV and to develop and test hypotheses to inhibit establishment of latency and reactivation, it is necessary to use human neurons. To this end, we have derived human neurons from induced pluripotent stem cells (iPSC) and established VZV latency and reactivation models. With these models we have already started to investigate the process leading to VZV latency.
Our results show that the VZV genome is progressively repressed, inhibiting transcription of its genes. We have also established a collaboration with Trine Mogensen (Aarhus University, Denmark) to determine the role that genetic polymorphisms on RNA polymerase III have on VZV infection, latency and reactivation of human neurons.
For the clinical aims we are recruiting a cohort of patients with VZV reactivation that will be followed clinically and where biomaterials will be ascertained for a biomarker search. Our preliminary data suggest that a metabolomics analysis of the cerebrospinal fluid can predict the complicating involvement of the central nervous system. We will also use data from the HSV cohort. The samples of the RESIST study with the general population of Hannover will serve as a control here.