Career Development Projects

CD001 DeFilippis

Chikungunya virus (CV) is a mosquito-transmitted virus endemic to tropical regions of Africa and Asia. Recently the virus has experienced a strong re-emergence and severe epidemics have occurred in European regions of the Mediterranean and Indian Oceans. Virus infection is associated with the development of severe arthritis that may persist for years after infection. Unfortunately, CV-specific vaccines do not exist and no therapies are approved for treatment of CV disease. Moreover, the long-neglected status of the virus as a research subject has led to a paucity of basic knowledge regarding aspects of the virus’ interaction with infected hosts including spread within a population, its vulnerability to the effects of the host immune system, and the molecular basis of arthritic disease. One thing that is known of related viruses is that they are highly susceptible to the effects of interferon, a molecule secreted by mammalian cells in response to microbial infection. Oddly, despite the detection of interferon in the bloodstreams of infected humans and animals, CV nevertheless grows and causes disease. The focus of our research is characterization of the molecular mechanisms that lead from the infection of human cells with CV to the synthesis and secretion from those cells of interferon. This includes identification of the cellular proteins that actually detect the virus itself as well as the downstream responses they initiate. In addition, we plan to further examine the ability of CV to withstand interferon-related antiviral effects triggered by host cells. The ultimate aim of this work is to generate new insights into the interaction of CV with its human host that may uncover therapeutic targets to be used for alleviation or eradication of CV-mediated disease.