We are in a unique position to identify novel primary immune deficiency factors increasing the susceptibility to alpha herpesvirus infections and leading to adverse disease progression. We combine complementary expertise on skin diseases, immunology, clinical neurology, virology, cell biology, and in particular, the combined genetic contribution of the host and the pathogens involved.
Our experience in cell culture systems to study the most relevant cell types for alpha herpesvirus infection; namely, keratinocytes, fibroblasts, immune cells and neurons will help us to build up experimental models to investigate different factors leading to enhanced susceptibility to viruses. We will determine whether the candidate factors identified through the patient cohort induce increased susceptibility to HSV-1 and -2, VZV, smallpox vaccination (MVA), or rhinovirus (RSV).
Towards this end, we develop a murine skin infection model to study the dynamics of HSV-1 spread within the skin, and from the skin to the nervous system. In this system, we will be able to manipulate potential host susceptibility factors, and to study their impact on the progression of viral skin infection. In addition, samples are currently being collected for the HSV cohort.