Alphaviruses, particularly chikungunya virus (CHIKV), represent a reemerging public health concern as mosquito vectors spread to new territories. While CHIKV typically causes an arthritogenic disease characterized by fever, rash, arthritis, and joint pain, a subset of individuals develops neurological disease, such as encephalitis, meningitis, and periphery neuropathy. Young children and the elderly are especially susceptible to developing neurological disease, and long-term neurological deficits can result in significant physical, emotional, mental, and financial disability. Despite this potential impact, very little is known about the neuropathogenesis of CHIKV infection. Further complicating matters is the strong evidence that the host’s immune system, rather than the virus itself, mediates much of the clinical disease and pathological changes in the brain. Our lab is taking a comprehensive approach to understanding the neuropathogenesis of CHIKV infection, using a combination of in vitro and in vivo methods to elucidate the specific mechanisms responsible for mediating disease and pathology. Subjects explored include the mechanisms mediating CHIKV neuroinvasion following infection in the periphery, how viral genetics mediate the divergent levels of virulence seen among different CHIKV strains, and the protective and pathogenic roles the immune response plays in CHIKV neuropathogenesis. The long-term goal of these studies is to identify the viral and host factors mediating disease induced by neurological CHIKV infection in order to develop effective therapeutics.
