Transcriptomics for a systems biology approach towards evidencebased immunomodulatory therapeutic strategies in current and novel viral epidemics

While HIV can be kept under control with proper antiviral treatment, there are no targeted antivirals for HTLV infections, and treatment currently relies on empirical use of immunomodulatory drugs. Many emerging infections are empirically treated with IFN before direct antivirals can be developed. A typical example is HCV, which is only recently curable in almost all patients with direct acting antivirals, while decades of empirical IFN treatment achieved mixed results. A good illustration of our lack of understanding IFN treatment is the so-called interferon paradox, since for the same disease, IFN can in some instances be beneficial and other instances detrimental for the host. We will investigate the antiviral and immunomodulatory pathways that are tipping the balance between asymptomatic infection and severe disease. These complex genome-wide findings will be translated into easy-to-use, clinically useful “metrics” that might enable personalized use of the currently available immunomodulatory drugs. We will focus on pandemic viral infections (HTLV-1, HCV and HIV-1), for which we hypothesize a central role for interferons/innate immunity in disease progression. Using a transcriptomics and systems biology approach on well-characterized cohorts of patients, we anticipate uncovering individualized and potential novel pathways that could be translated into immunotherapeutic or immunoprophylactic strategies in current, emerging and possibly novel viral epidemics.