Sat. May 21st, 2022

Abstract

Vesicular stomatitis Indiana virus (VSV) recombinant is the most common cause of vesicular disease outbreaks in cattle throughout the Western Hemisphere. Two main serotypes, Indiana and New Jersey, cause epidemic diseases in swine, cattle, and horses. We generated recombinant viruses derived from the Indiana serotype genome that were engineered to contain and express: (1) a single copy of the Indiana serotype glycoprotein gene (VSIV-GI); (2) a single copy of the New Jersey serotype glycoprotein gene (VSIV-GNJ); or (3) two copies of the glycoprotein gene, one from each of the two major VSV serotypes (VSIV-GNJGI) [Martinez I, Rodriguez LL, Jimenez C, Pauszek SJ, Wertz GW.

The vesicular stomatitis virus glycoprotein is a determining factor in the pathogenesis in pigs, a natural host. J Virol 2003;77(14):8039-47]. These recombinant viruses and a highly pathogenic New Jersey field isolate (VSNJV), from which the GNJ gene was derived, were inoculated into pigs, a natural host, and tested for the induction of neutralizing antibodies to both serotypes. The neutralizing antibody response induced by VSIV-GI, VSIV-GNJ, and VSNJV was serotype-specific, depending on the glycoprotein expressed.

VSIV-GNJGI expressed both glycoproteins stably through multiple rounds of replication in pigs and induced neutralizing antibodies against both VSV serotypes, with a predominance of the Indiana serotype in the serological response. Pigs immunized with VSIV-GI or VSIV-GNJ were protected against exposure to high doses of homologous viruses. Pigs inoculated with VSIV-GNJGI were protected against challenge with VSIV-GI, but three of four animals developed lesions after challenge with the highly pathogenic field isolate from New Jersey.

Significance

Vesicular Indiana stomatitis virus (VSIV) is a veterinary pathogen that is also used as the backbone for many vaccine and oncolytic strategies. In natural and therapeutic settings, viral infections such as VSIV are detected by the host, and as a result, host cells produce proteins that can protect them from viruses. In the case of VSIV, these antiviral proteins restrict viral replication and protect most healthy tissues from virus infection.

To understand how VSIV causes disease and how healthy tissues are protected from VSIV-based therapies, it is crucial that we identify the proteins that inhibit VSIV. Here, we show that TRIM69 is an antiviral defence that can potently and specifically block VSIV infection.