Project 466868

Human Herpesvirus 6A/B (HHV6A/B) are two viruses currently present in over 90% of our population, remaining in the body for life following infection. The consequences of this are not well characterized or understood, but there may be associations between infection with HHV6A/B and later-onset neurological disease, for example multiple sclerosis, epilepsy, and even brain cancer. Given the nature of infection being in the brain, studying HHV6A/B can be challenging as tissue is not readily accessible. However, we are now able to use stem cells to create the different cells that make up the brain, combining them to create a 3D co-culture of different brain cell types to mimic the real thing. The Muffat Lab at the Hospital for Sick Children recently pioneered the creation of microglia from stem cells, which are the immune cells of the brain and thus of utmost importance for studying viral infection response. For the first time, it is possible to investigate infection of HHV6A/B and the role of microglia in the immune response in a readily accessible primary human model wherein all the key cell types are present in a structurally similar environment to where native infection occurs. This model can then be used to study disease, in this case, the immune response of each cell type as well as a combination of each following infection with HHV6A/B. Understanding the mechanisms by which a pathogen present in almost the entire population infects and affects the central nervous system will provide fundamental insight into HHV6A/B biology, as well as the onset of neurological conditions it is associated with. My research will uncover the roles of neural and glial cells following HHV6A/B infection in a novel model system that closely mimics human brain composition and architecture.