Sensitivity to BST-2 restriction correlates with Orthobunyavirus host range

TY - JOUR

T1 - Sensitivity to BST-2 restriction correlates with Orthobunyavirus host range

AU - Varela, Mariana

AU - Piras, Ilaria M

AU - Mullan, Catrina

AU - Shi, Xiaohong

AU - Tilston-Lunel, Natasha L

AU - Pinto, Rute Maria

AU - Taggart, Aislynn

AU - Welch, Stephen R

AU - Neil, Stuart J D

AU - Kreher, Felix

AU - Elliott, Richard M

AU - Palmarini, Massimo

N1 - Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2017/9

Y1 - 2017/9

N2 - 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.

AB - 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.

KW - Animals

KW - Antigens, CD/metabolism

KW - Antigens, Differentiation, B-Lymphocyte/metabolism

KW - Cell Line

KW - GPI-Linked Proteins/metabolism

KW - Host Specificity

KW - Host-Pathogen Interactions

KW - Humans

KW - Orthobunyavirus/immunology

KW - Sheep

KW - Viral Envelope Proteins/antagonists & inhibitors

KW - Virus Release

U2 - 10.1016/j.virol.2017.06.017

DO - 10.1016/j.virol.2017.06.017

M3 - Article

C2 - 28628828

SN - 0042-6822

VL - 509

SP - 121

EP - 130

JO - Virology

JF - Virology

ER -