Aarhus University Hospital, Denmark
Student: Alon Schneider Hait, M.D., Ph.D. fellow
Supervisor: Prof. Trine H Mogensen, M.D., Ph.D.
Co-supervisor: Prof. Søren Riis Paludan, Ph.D.
Recurrent benign lymphocytic meningitis (RBLM) is a viral infectious disease of the brain and its covering membranes, caused by herpes simplex virus type 2 (HSV-2). The disease is characterized by recurent episodes of headache, photophobia (eye discomfort when exposed to light), fever and stiffness of the neck. The episodes are self-limited, but the sufferer remains with neurological deficits as consequence of the disease. The pathway in which the disease is installed is unknown, and so far the patients remain with insufficient information regarding their disease and its causes.
In this study, we hypothesize that an inborn genetic defect in the patient’s DNA can explain at least part of the disease pathway, by causing the host to react inappropriately to the viral invasion, or to be unable to suppress viral replication in case of reactivation. In this study, we have characterized inclusion criteria for selection of our study group, by collaboration with other medical doctors and medical centers in Europe we have gathered 15 patients suffering from RBLM and after gaining informed consent, we have collected blood from them. DNA from patients’ blood was sent to whole-exome sequencing, a process in which the entire coding genome of the person is being scanned for genetic variations from the “normal”, and primary peripheral blood mononuclear cells (PBMCs) were isolated from whole blood.
Functional studies were then performed by infecting the cells with HSV-2 virus and stimulation cells with DNA and RNA mimic molecules to observe their anti-viral and pro-inflammatory response, looking for functional deficiency. After receiving the genetic sequencing, we have placed the raw data into bioinformatic filters, and concluded a short list of genetic variants, which share a common pathway, related to autophagy.
In the future, we wish to characterize those variants further and to conclude if the genetic variant is in fact disease causing.
Trine H Mogensen, Associate professor
Department of Infectious Diseases
Aarhus University Hospital Skejby
Palle Juul-Jensens Boulevard 99
DK-8200 Aarhus N