Abstract

Orthobunyaviruses include several recently emerging viruses of significant medical and veterinary importance. There is currently very limited understanding on what determines the host species range of these pathogens. In this study we discovered that BST -2, an interferon stimulated gene also known as tetherin, restricts orthobunyavirus replication in a host-specific manner. We show that viruses with human tropism (Oropouche virus and La Crosse virus) are restricted by sheep BST -2 but not by the human orthologue while viruses with ruminant tropism (Schmallenberg virus and others) are restricted by human BST -2 but not by the sheep orthologue. Cache valley virus, an orthobunyavirus known to infect both sheep and humans is not restricted by either BST -2 orthologues. This is the first study identifying a host determinant of species susceptibility to bunyavirus infection. This work provides critical insight to help us dissect the adaptive changes that bunyaviruses require to cross the species barrier and emerge into new species.