Orthobunyaviruses: From Virus Binding to Penetration into Mammalian Host Cells.

Stefan Windhaber,Pierre-Yves Lozach,Qilin Xin

doi:10.3390/v13050872

Abstract

With over 80 members worldwide, Orthobunyavirus is the largest genus in the Peribunyaviridae family. Orthobunyaviruses (OBVs) are arthropod-borne viruses that are structurally simple, with a trisegmented, negative-sense RNA genome and only four structural proteins. OBVs are potential agents of emerging and re-emerging diseases and overall represent a global threat to both public and veterinary health. The focus of this review is on the very first steps of OBV infection in mammalian hosts, from virus binding to penetration and release of the viral genome into the cytosol. Here, we address the most current knowledge and advances regarding OBV receptors, endocytosis, and fusion.

Highlights

Orthobunyavirus consists of over 80 members that are globally distributed, which is a genus of the family Peribunyaviridae (Bunyavirales order) along with Herbevirus, Pacuvirus, and Shangavirus (Table 1) [1]
dendritic cells (DCs)-SIGN was shown to enhance infection by rhabdoviral particles pseudotyped with La Crosse virus (LACV) glycoproteins [50], indicating that the interactions between OBVs and the lectin most likely occur through the glycans carried by Gn and Gc
Studies using complementary approaches aiming to impair the function of adaptor protein 2 (AP2) and clathrin chains, i.e., those based on the use of drugs, dominant negative (DN) mutants, and small interfering RNAs, highlighted the dependance of Akabane virus (AKAV), LACV, Oropouche virus (OROV), and other OBVs on clathrin-mediated endocytosis (CME) for infection [53,55,56]

Summary

Introduction

Orthobunyavirus consists of over 80 members that are globally distributed, which is a genus of the family Peribunyaviridae (Bunyavirales order) along with Herbevirus, Pacuvirus, and Shangavirus (Table 1) [1]. Valley virus in the United States of America (USA) and Schmallenberg virus (SBV), an orthobunyavirus that emerged in 2011 in Central Europe, are both teratogenic in livestock, predominantly in ruminants [8,9,10]. A growing body of evidence indicates that genetic reassortment between OBV members can occur in arthropod vectors [15,16]. The frequency of such events remains unknown in the wild, but it certainly contributes to the emergence of new viruses with potentially significant pathogenicity in humans. Most information on OBVs derives from a limited number of studies and an even smaller number of isolates, mainly BUNV, California encephalitis virus (CEV), LACV, and SBV (Table 1). For information on OBVs and their arthropod vectors, we recommend reviewing [2,3,7,17,18,19,20,21]

OBV Genome and Viral Particles

Receptors for OBVs in Mammalian Hosts

OBV Uptake

OBV Intracellular Trafficking

OBV-Cell Membrane Fusion and Penetration

Conclusions and Perspectives