Inflammation and Viral Insults/Infection with Human Herpes Virus 6 (HHV6)
Whole virions can be found in hOPC after infection.
This project is focused on determining the effect of the human herpesvirus 6 (HHV-6) on oligodendrocyte progenitor cells (OPCs). Uniquely among the human herpesviruses, new data show that HHV6 maintains or establishes its latency state via chromosomal integration into the host genome. Importantly, chromosomal integration of both HHV-6A and B strains occurs in 1% of live births and has been associated with a number of pathologies ranging from chronic fatigues syndrome to impairment of mental functioning. The mechanisms underlying these defects are not known.
With the recent discovery of a viral protein that is exclusively expressed during the latency state while the viral is integrated into the genome, it became possible to study the impact of latent HHV6 infections on cellular functions.
We have presented evidence, that HHV-6 can infect human OPCs. A restricted infection with whole virus causes cell cycle arrest and impaired differentiation. As infection with whole virus can lead to latency and viral integration, we are currently pursuing the hypothesis that latent infection of hOPC with HHV6 also impairs hOPCs function. We use transplantation of infected hOPCs into experimentally induced demyelinating lesions to determine the impact of HHV6 on the hOPCs ability to contribute to the repair process. We are also using genetic tools to determine the signaling pathways that might be disrupted in hOPCs by integrated HHV6.
This project is conducted in collaboration with Dr. David Mock, a Department associated Physician-Scientists who is an expert in infectious immune diseases and Dr. Chris Proschel, who is overseeing aspects of human cell generation and infections.