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.
The advent of improved biomarkers promises to enhance the clinical care for patients with DENV infections. In an effort to identify an immunologic biomarker for use in managing DENV patients, we will try to assess the type I and III IFN blood signatures during the acute phase of DENV positive patients. Indeed, through the analysis of the factors relative to IFN pathways, we enable to identify an IFN module that can be employed to predict disease activity. Thus, even if this project is a proof-of-concept, our approach lays the foundation for the development of immunologic `IFN signatures¿ that could be useful in predicting DENV disease course. We firmly believe that the clinical management with DENV might be enhanced by the development of improved biomarkers, which could assist clinicians in assessing disease activity and predicting long-term disease outcomes. Moreover, this project is based entirely on clinical research on DENV positive patients and uses a simple, but innovative, scientific approach that makes sure it will get off the ground quickly ¿ and achieve to preliminary results faster. Lastly, it could provide future fundamentals for the development of a patent on specific IFN gene signature biomarkers that are useful for identifying DENV positive patients who are most likely to exhibit a severe clinical outcome of disease. The future disclosure could also provide methods and assay for testing blood samples for the biomarkers, as well as procedures/guidelines for the clinical management of the DENV patients based on the test results.