The major interest of the laboratory is the molecular pathogenesis of RNA virus infections, with an emphasis on mosquito-transmitted viruses. Mosquito-transmitted RNA viruses include flaviviruses, such as Dengue virus and West Nile virus, bunyaviruses, such as Rift Valley fever virus, and alphaviruses, such as chikungunya virus and Ross River virus. Chikungunya virus, Ross River virus, and related arthritogenic alphaviruses cause explosive epidemics that can involve thousands to millions of infected patients and are an emerging disease threat. Chikungunya, which translates as “disease that bends up the joints”, is characterized by an abrupt onset of fever with severe joint pain, and the pain may persist for weeks to years. Chronic chikungunya joint disease, and the chronic rheumatological diseases caused by the related arthritogenic alphaviruses, may result from persistent infection in musculoskeletal tissues.
To answer our scientific questions, we use genetic strategies, molecular and cellular approaches, and mouse models of acute and chronic chikungunya virus or Ross River virus infection. Using these systems, we study the interface of viruses with the host immune response. We are particularly interested in defining mechanisms of activation and resolution of virus-induced inflammatory responses, immunological mechanisms that control virus clearance versus virus persistence, and viral genetic determinants that counteract host anti-viral responses and promote persistent infection. The mouse models we have developed enable us to utilize transgenic and knockout strains to study the role of specific host genes in the disease process and investigate the genetics of host susceptibility to acute and chronic infection. Additionally, due to the well-established alphavirus reverse genetics system, we are able to easily manipulate the genome of the virus. Taken together, these advantages provide a highly tractable system to establish mechanisms by which viral interactions with the host lead to disease. In addition, we utilize cell culture-based and animal infection models to test novel anti-virals and immunomodulatory therapeutics against acute and chronic CHIKV/RRV infection.