Hunter Thornton Rose Hills
Unraveling Novel Mechanisms of Dengue Virus RNA Capping and Immune Evasion
Mosquito-borne diseases are a major burden to public health systems, especially in developing countries. It is estimated that about 3.9 billion people worldwide are at risk of infection with dengue virus, with 50-100 million cases per year1. Nonetheless, safe vaccines and therapeutics for dengue are not available. Transmission occurs through the bite of female Aedes mosquitos infected with one of four antigenically related dengue virus serotypes (DENV1-4). Infection with one serotype may confer temporal protection or, conversely, enhance disease of a subsequent infection with a different serotype, suggesting an important role for immune responses in driving the outcome of the disease24. The mechanisms that govern DENV replication and its interplay with the immune system are a major knowledge gap in the field. Here, we address this issue by investigating the viral non-structural protein NS5, known to be involved in both viral replication and immune evasion mechanisms. In particular, we aim to characterize conserved amino acids within the NS5 protein to determine their prospective roles in viral RNA replication and immunostimulation. This knowledge will inform the design of live-attenuated vaccines with improved immunogenic properties, thus alleviating the burden of dengue worldwide.