An optimized RNA polymerase II minigenome system for Nipah virus

Abstract

Nipah virus is a highly lethal, zoonotic paramyxovirus that has caused recurring outbreaks in several South and Southeast Asian countries since its discovery in Malaysia in 1998. Symptoms of infection include severe respiratory and neurological disease, often resulting in death. As no approved vaccines or antivirals are currently available to reduce the burden of this virus, it is classified as a biosafety level 4 pathogen. There is an urgent need for systems that enable research in a lower biocontainment setting, especially since the World Health Organization declared Nipah virus a priority pathogen for pandemic concern. In the past, several minigenome systems have already been developed as safe alternatives to working with infectious virus; however, these systems remain relatively inefficient and lack robustness and reliability for further applications. Therefore, we developed novel optimized RNA polymerase II-driven minigenomes with nanoluciferase or enhanced green fluorescent protein reporter genes. Both systems outperform previously designed Nipah virus minigenomes, are easily operable, and can be implemented for antiviral compound screenings.