Abstract

Bovine viral diarrhea virus (BVDV), a pestivirus which exists in the two distinct species BVDV-1 (syn. Pestivirus A) and BVDV-2 (syn. Pestivirus B), is the causative agent of one of the most widespread and economically important virus infections in cattle. For economic as well as for animal health reasons, an increasing number of national BVDV control programs were recently implemented. The main focus lies on the detection and removal of persistently infected cattle. The application of efficient marker or DIVA (differentiation of infected from vaccinated animals) vaccines would be beneficial for the eradication success in regions with a high BVDV prevalence to prevent fetal infection and it would allow serological monitoring of the BVDV status also in vaccinated farms. Therefore, a marker vaccine based on the cytopathic (cp) BVDV-1b strain CP7 was constructed as a synthetic backbone (BVDV-1b_synCP7). For serological discrimination of vaccinated from infected animals, the viral protein Erns was substituted by the heterologous Erns of Bungowannah virus (BuPV, species Pestivirus F). In addition, the vaccines were attenuated by a deletion within the type I interferon inhibitor Npro protein encoding sequence. The BVDV-2 vaccine candidate is based on the genetic sequence of the glycoproteins E1 and E2 of BVDV-2 strain CS8644 (CS), which were introduced into the backbone of BVDV-1b_synCP7_ΔNpro_Erns Bungo in substitution of the homologous glycoproteins. Vaccine virus recovery resulted in infectious cytopathic virus chimera that grew to titers of up to 106 TCID50/mL. Both synthetic chimera BVDV-1b_synCP7_ΔNpro_Erns Bungo and BVDV-1b_synCP7_ΔNpro_Erns Bungo_E1E2 BVDV-2 CS were avirulent in cattle, provided a high level of protection in immunization and challenge experiments against both BVDV species and allowed differentiation of infected from vaccinated cattle. Our study presents the first report on an efficient BVDV-1 and -2 modified live marker vaccine candidate and the accompanying commercially available serological marker ELISA system.

Highlights

  • Bovine viral diarrhea virus (BVDV) infection is one of the most important diseases of cattle stock worldwide with an enormous economic and animal welfare impact on beef and dairy industries [1]

  • Full synthetic bovine viral diarrhea (BVD) viruses based on the genetic background of the cytopathic BVDV-1b strain

  • The availability of a DIVA-compatible BVD vaccine is an important pillar in disease eradication programs

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Summary

Introduction

Bovine viral diarrhea virus (BVDV) infection is one of the most important diseases of cattle stock worldwide with an enormous economic and animal welfare impact on beef and dairy industries [1]. Analysis revealed at least 21 subtypes within BVDV-1 and within BVDV-2 [14] Both species occur in two biotypes, namely noncytopathic (ncp) and cytopathic (cp) viruses, according to their ability to induce apoptosis in infected cell culture [15]. Infection of pregnant animals during the first trimester with ncp viruses of both species may cause fetal death or the birth of persistently infected (PI) calves [17]. These immunotolerant carriers shed livelong virus in high amounts and serve as the primary reservoir for BVDV in all cattle populations worldwide [14,18,19]

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