Functional study of the kinases related with dengue infection

• Grant number: 14/01162-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2014
• End date: May 31, 2017
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Lucio Holanda Gondim de Freitas Junior
• Grantee: Bruno dos Santos Pascoalino
• Host Institution: Fundação Butantan

Abstract

Viral pathogens have a specialized biological system that allows them to infect their hosts and utilize the cellular machinery in its favor. Viruses are widely known to infect and submit the host cell to their purpose, using the cellular machinery to facilitate replication of their genome, and thereby promoting their proliferation into the host cell. Dengue is an important world health issue since its re-emergence in the last 50 years. Dengue viruses (DENV) are responsible for a tropical hemorrhagic fever that affects more than two thirds of the world's population. The lack of an effective vaccine or drugs results in half a million people dengue infections every year. Due to failure in discovering and developing efficient vaccines and drugs focusing the virus itself, others approaches must be taken into account, such as virus and host interaction. Protein kinases are among the largest and most well-studied gene families. Protein phosphorylation plays an essential role in intercellular communication in eukaryotic organisms by mediating signal transduction during development, transcription, immune response, metabolism, apoptosis, and cell differentiation. Protein kinases are one of the most important families of therapeutic targets with broad implications in cancer, inflammation and many other diseases.Aberrant regulation of kinases plays a causal role in many diseases, and is usedin several pathogenesis for their proper development into their host, for example the DENV. The molecular details of host-virus interactions taking place during flaviviral infection remain mostly unknown. The recent development of genome-scale siRNA screens to identify host factors required for viral propagation has shed light on the complexity of these interactions, moreover protein kinases has been reported to be important for viral development in the host cell. By this reason the study of these proteins and their functions will contribute to the discovery and development of new therapeutics.