Characterization of Bunyamwera, Batai, and Ngari Viruses: Unrecognized Arboviruses of One Health Importance in Rwanda

Bunyamwera (BUNV), Batai (BATV), and Ngari (NRIV) are mosquito-borne viruses (Genus: Orthobunyavirus, Family: Peribunyaviridae, Order: Bunyavirales). They have an RNA tripartite genome consisting of small (S), medium (M), and large (L) segments. NRIV is a natural reassortant of BUNV and BATV, with the genome: SBUNV, MBATV, LBUNV. All three viruses have been associated with disease of varying severity in domestic ruminants and humans. In livestock, infection with these viruses is associated with abortions, while humans may present a mild febrile illness or severe disease such as hemorrhagic fever or meningoencephalitis. In East Africa, BUNV, BATV, and NRIV co-circulate and present similar clinical manifestation with Rift Valley Fever virus (RVFV), another Bunyavirus (Genus: Phlebovirus, Family: Phenuibunyaviridae) of critical importance in this region as it is associated with massive economic losses in livestock production and cases of human death. In Rwanda, although RVFV is known to circulate in livestock, whether these other Bunyaviruses co-circulate remains to be determined. The overall goal of this research is to describe and compare the in vitro and in vivo characteristics of BUNV, BATV, and NRIV. To achieve this objective, we a) comparatively characterized in vitro infection kinetics in Vero cells, b) comparatively characterized in vivo infection kinetics in C57BL/6 mouse model and quantified potential cross-neutralization of resulting antibody, and c) developed a disease progression model for BUNV infection in IRF3/7-/--/- mice. Further, we hypothesized that these Orthobunyaviruses circulate in Rwanda and cause infections that are misclassified as RVFV cases. We found: 1) all viruses are stable in extracellular conditions up to 30 days but inactivation by a commonly used detergent is successful; 2) C57BL/6 mouse infection is not a robust infection model; 3) there are varying degrees of cross-neutralization among the viruses; 4) BUNV infection in IRF3/7-/--/- mice may provide hemorrhagic fever infection model; and 5) these viruses co-circulate with RVFV in Rwanda. This study is the second report of BATV in Africa, the first to detect these viruses in Rwanda, and the first report of co-infection with BUNV and BATV, providing insight into the provenance of the reassortant NRIV