title: Assessment of a novel recombinant vesicular stomatitis virus with triple mutations in its matrix protein as a vaccine for pigs.
abstract: Vesicular stomatitis virus (VSV) causes a serious vesicular disease responsible for economic losses in the livestock industry. Currently, there are no suitable vaccines to prevent VSV infection. Although the structural matrix (M) protein of VSV has been shown to be a virulence factor in rodent models, its role in the pathogenicity of VSV infection in livestock species is unknown. We hypothesized that VSV with mutations in the M protein represents a novel live attenuated vaccine candidate. To test this, we introduced mutations into VSV M protein using reverse genetics and assessed their attenuation both in vitro and in pigs, an important natural host of VSV. A recombinant VSV with a triple amino acid mutation in M protein (VSVMT) demonstrated a significantly reduced ability to inhibit the type I interferon (IFN) signaling pathway and to shutoff host gene expression compared to WT-VSV and a mutant virus with a single amino acid deletion (VSVΔM51). Inoculation of pigs with VSVMT induced no apparent vesicular lesions but stimulated virus-neutralizing antibodies and animals were protected against virulent VSV challenge infection. These data demonstrate that the M protein is an important virulence factor for VSV in swine and VSVMT represents a novel vaccine candidate for VSV infections in pigs.
authors.affiliation: School of Agriculture and Biology, Shanghai JiaoTong University, 800 Dongchuan Rd., Shanghai 200240, China; Shanghai Municipal Veterinary Key laboratory, 800 Dongchuan Rd., Shanghai 200240, China.
authors.forename: Xinkui
authors.initials: X
authors.lastname: Fang
authors.affiliation: School of Agriculture and Biology, Shanghai JiaoTong University, 800 Dongchuan Rd., Shanghai 200240, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Qi
authors.affiliation: School of Agriculture and Biology, Shanghai JiaoTong University, 800 Dongchuan Rd., Shanghai 200240, China; Shanghai Municipal Veterinary Key laboratory, 800 Dongchuan Rd., Shanghai 200240, China.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Ma
authors.affiliation: School of Agriculture and Biology, Shanghai JiaoTong University, 800 Dongchuan Rd., Shanghai 200240, China.
authors.forename: Xinchu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: School of Agriculture and Biology, Shanghai JiaoTong University, 800 Dongchuan Rd., Shanghai 200240, China; Shanghai Municipal Veterinary Key laboratory, 800 Dongchuan Rd., Shanghai 200240, China.
authors.forename: Shikuan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: School of Agriculture and Biology, Shanghai JiaoTong University, 800 Dongchuan Rd., Shanghai 200240, China; Shanghai Municipal Veterinary Key laboratory, 800 Dongchuan Rd., Shanghai 200240, China. Electronic address: taosun99@hotmail.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D020125:Mutation, Missense; D018353:Rhabdoviridae Infections / Q000517:prevention & control / Q000662:veterinary*; D013552:Swine; D013553:Swine Diseases / Q000517:prevention & control* / Q000821:virology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D018116:Vesiculovirus / Q000235:genetics / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C094460:M protein, Vesicular stomatitis virus; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins; D014765:Viral Vaccines; D037521:Virulence Factors
keywords: Matrix protein; Pig; Vaccine; Vesicular stomatitis virus