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Alfredo Castello

MRC Career Development Fellow

Understanding the role of RNA-binding proteins in virus infection

Our overarching goal is to elucidate how cellular RNA-biding proteins (RBPs) control virus infection. Millions of people die every year due to infections by RNA viruses, representing a major threat for human health and a burden on economies and infrastructure. Therefore, it remains critical to improve our understanding of the mechanisms underpinning virus infection. As RNA genomes are small, viruses rely on host resources to complete their biological cycle and this dependence represents great opportunities for antiviral intervention. In this context, cellular RBPs emerged as central players of virus infection as they are essential for replication, processing, translation and packaging of viral RNAs. On the other hand, RBPs are key components of the antiviral arsenal of the cell, sensing viral RNA to trigger the host defence mechanisms. My laboratory employs new system-wide methods to uncover the complement of cellular RBPs that play central roles in virus infection, using human immunodeficiency virus (HIV) and sindbis virus (SINV) as discovery models. Our work uncovered dozens of RBPs that are crucial for viruses, and we are currently investigating their mechanisms of action by applying cutting-edge RNA biology, virology and fluorescence and electron microscopy methods. We envision that the inhibition of these RBPs may afford the development of new antivirals.