Characterization of genetic reassortment and recombination potentials between Arumowot Virus and MP-12 vaccine strain

Rift Valley fever virus (RVFV) is a zoonotic arbovirus that causes significant morbidity and mortality in both humans and animals. In humans, the disease manifests itself as febrile illness, hemorrhagic fever, encephalitis, or retinitis. In animals, RVFV causes high rates of abortions and fetal malformations. Since the first Rift Valley fever (RVF) outbreak in 1930, there have been several major outbreaks across Africa and the Middle East. Effective control of RVF outbreaks via vaccination is important for both endemic and non-endemic countries. In some countries in Africa, inactivated and/or live-attenuated vaccines have been available for vaccinations of susceptible ruminants. In the U.S., a live-attenuated MP-12 vaccine strain was conditionally licensed for animal use, whereas it is also an Investigational New Drug for clinical trials. Upon the field trials of live-attenuated RVF MP-12 vaccine, potential formations of reassortant or recombinant strains between a vaccine strain and circulating pathogenic RVFV strains or other phleboviruses should be characterized. My central hypothesis is that genetic reassortment or recombination between two phleboviruses can occur when a loss or swap of gene element does not deteriorate the viability of resulting viruses. The overall objective of this study is to analyze genetic reassortment or recombination between RVFV MP-12 strain and AMTV, using coinfection assays and reverse genetics. The long-term goal is to establish a universal method to develop a novel pseudotype chimeric virus system applicable for most pathogenic phleboviruses. To address the central hypothesis, the following three aims are proposed. Specific Aim 1: Characterization of genetic reassortment between MP-12 strain and the genetic variant, rMP12- GM50, and between MP-12 strain and Arumowot virus, Specific Aim 2: Characterization of the attenuation and protective efficacy of rMP12-GM50 strain in mice, and Specific Aim 3: Characterization of recombinant MP-12 strain with AMTV genetic elements. Overall, the study will characterize potential occurrence of interspecies reassortment and recombination between RVFV and AMTV, and evaluate the significance of the presence of AMTV in RVF vaccination in endemic countries.