Ricerc@Sapienza

Despite vast improvements in medicine and health care, humans still suffer unpredictably from epidemics of infectious disease. An example of emerging infectious disease resulting in a wide variation in clinical presentations and outcomes are those caused by a mosquito-borne flavivirus, dengue virus (DENV). Disease severity and pathogenesis of DENV infection in humans depend on many factors, including pre-existing immunity, strain virulence, host genetics and virus-host interactions. Among the DENV-host interactions, viral evasion strategies identified from in vitro studies to overcome type I interferon (IFN)-mediated immunity have a critical role in modulating pathogenesis. Type III IFN (IFN¿) response seems to be also involved in driving the immunopathogenesis of DENV, although the evidences are rather limited and no data are available on in vivo IFN¿s expression and IFN¿ genetic variations. Since clinical management of DENV positive patients is often hampered by their heterogeneous nature in both clinical presentation and outcome, a multidisciplinary approach should be considered for identify reliable biomarkers to be used in clinical practice, and an analysis of the factors related to IFN activation should be carefully planned. With this purpose, we plan to perform a comprehensive examination of type I and III IFN activation in DENV infection, by integrating virological and clinical data with those on IFN gene signatures and IFN-genetic variations.