Sensitivity to BST-2 restriction correlates with Orthobunyavirus host range

Mariana Varela*, Ilaria M. Piras, Catrina Mullan, Xiaohong Shi, Natasha L. Tilston-Lunel, Rute Maria Pinto, Aislynn Taggart, Stephen R. Welch, Stuart J.D. Neil, Felix Kreher, Richard M. Elliott, Massimo Palmarini

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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/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. We also show that BST-2 blocks orthobunyaviruses replication by reducing the amount of envelope glycoprotein into viral particles egressing from infected cells. This is the first study identifying a restriction factor that correlates with species susceptibility to orthobunyavirus infection. This work provides insight to help us dissect the adaptive changes that bunyaviruses require to cross the species barrier and emerge into new species.

Original languageEnglish
Pages (from-to)121-130
Number of pages10
Early online date17 Jun 2017
Publication statusPublished - 1 Sep 2017


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