The Relationship between reassortment and Oropouche virus pathogenicity

PROJECT SUMMARY/ABSTRACT Oropouche virus (OROV) is an emerging arbovirus and a significant public health issue in Central and South America. Since the early 1960s, over half a million infections have been documented. However, the actual numbers are likely much higher due to the lack of an adequate differential diagnostic system. OROV has a tri- segmented negative-sense RNA genome made up of Small (S), Medium (M), and Large (L) segments. S encodes the nucleoprotein, M encodes the glycoproteins, and L encodes the RNA-dependent RNA polymerase. The glycoproteins are responsible for viral entry into host cells and are targets for neutralizing antibodies. The segmented nature of the genome allows OROV to exchange segments with co-infecting viruses through a process known as reassortment. Reassortment is responsible for antigenic shifts in influenza viruses, which is critical for the emergence of pandemic strains. Such effects on bunyaviruses, including OROV, are poorly understood. This is a deficit since three known OROV reassortants are circulating in South America. These reassortants differ in their glycoproteins, which could influence host tissue tropism, immune evasion, and vector competency. The goal of this project is to investigate how reassortment modulates OROV virulence. Aim 1 will use in vitro methods to identify phenotypic changes within the reassortants due to the different glycoproteins. Aim 2 will investigate the reassortants' virulence compared to OROV using a murine model. These studies are significant as they will provide critical data for future studies to (a) assess the threat of OROV and OROV reassortants to public health and (b) develop pan-OROV antiviral therapeutics and vaccines.