Vesicular Stomatitis Virus: From Agricultural Pathogen to Vaccine Vector

Abstract

Vesicular stomatitis virus (VSV), which belongs to the Vesiculovirus genus of the family Rhabdoviridae, is a well studied livestock pathogen and prototypic non-segmented, negative-sense RNA virus. Although VSV is responsible for causing economically significant outbreaks of vesicular stomatitis in cattle, horses, and swine, the virus also represents a valuable research tool for molecular biologists and virologists. Indeed, the establishment of a reverse genetics system for the recovery of infectious VSV from cDNA transformed the utility of this virus and paved the way for its use as a vaccine vector. A highly effective VSV-based vaccine against Ebola virus recently received clinical approval, and many other VSV-based vaccines have been developed, particularly for high-consequence viruses. This review seeks to provide a holistic but concise overview of VSV, covering the virus's ascension from perennial agricultural scourge to promising medical countermeasure, with a particular focus on vaccines.

Keywords: Ebola virus; VSV; VSV-EBOV; countermeasure; medical countermeasure; reverse genetics; vaccine; vesicular stomatitis virus.

Figure 1

The structure of VSV and its genome. A diagram of the characteristically bullet-shaped virion is shown above a representation of the VSV genome. The negative-sense, single-stranded RNA genome (depicted in blue within the virion) is completely encapsidated by the nucleoprotein (N), which, together with the phosphoprotein (P) and the RNA-dependent RNA polymerase (L), forms the nucleocapsid or ribonucleoprotein complex. The matrix protein (M) condenses the nucleocapsid and drives virion budding. The glycoprotein (G) studs the surface of the virion and exists in trimeric complexes. This figure was created with BioRender.com.

Figure 2

Recombinant VSVs. (A) Manipulation of the VSV genome results in recombinant VSVs (rVSVs) that can be used for a variety of purposes. Most rVSVs contain additional transgenes (i.e., transgene X or Y)—often in place of VSV G—that drive the expression of additional proteins, including other viral glycoproteins or reporter molecules. Insertion of one or more transgenes is flexible and can be accommodated at almost any position within the genome. (B) Replication-competent rVSVs result when the added transgene supports virus replication. For example, in the case of VSV-EBOV, the EBOV GP replaces VSV G but is still sufficient to facilitate the VSV replication cycle [49]. VSV-EBOV-GFP expresses GFP in addition to EBOV GP [50], while VSV-EBOV-NiV G expresses both EBOV GP and the NiV attachment glycoprotein [51]. (C) Replication-incompetent rVSVs result when the added transgene cannot support virus replication. For example, replacement of VSV G with GFP results in a virus that must be pseudotyped with a glycoprotein in order to be infectious [52]. Similarly, NiV G is unable to facilitate virus replication in the absence of VSV G [53]. This figure was created with BioRender.com.