Chicago - 12:00 PM - 1:00 PM
The Department of Microbiology-Immunology Seminar Series
"Reprogramming of Brain Function by Neurotropic Viruses"
Robyn Klein, MD, PhD - Washington University, St. Louis
This seminar will address neuroimmune interactions that underlie virus-mediated cognitive loss during recovery from infection with neurotropic viruses. Members of the Flavivirus genus, which include West Nile (WNV), Japanese encephalitis (JEV), and Zika (ZIKV) viruses,are the most important arthropod-borne viruses causing encephalitis in humans. Acutely, patients suffering from WNV neuroinvasive disease (WNND) can experience confusion, fatigue, loss of motor control, memory loss, coma, and a mortality rate of 5-10%. WNV is a (+)-sense single-stranded RNA virus that targets fully differentiated neurons, but may be cleared by immune-mediated processes, even after infection of the central nervous system (CNS). Animal studies have identified multiple cytokines that play critical roles in cell-mediated antiviral immunity, including tumor necrosis factor (TNF)a, type I, II and III interferons (IFNs), and interleukin (IL)-1, which improve survival. However, approximately half of survivors experience debilitating, long-term cognitive sequelae, including defects in verbal and visuospatial learning, for months to years beyond the acute infectious event. While neuronal death is associated with high mortality in human and murine cases of WNV encephalitis, survivors may exhibit limited neuronal loss, suggesting inflammatory processes triggered acutely contribute to long-term memory dysfunction. Here, will be presented several inflammatory-mediated mechanisms that lead to alterations in neural correlates of memory that promote defects in spatial learning. These studies identify putative and, possibly, generalizable mechanisms for CNS dysfunction in an array of neurologic diseases, and raise the possibility that their neuropathogenesis might include infectious triggers.