Identification of a Common Conformational Epitope on the Glycoprotein E2 of Classical Swine Fever Virus and Border Disease Virus.

Yu-Liang Huang,Helen Crooke,Chia-Yi Chang,Alexander Postel,Chia-Huei Yang,Denise Meyer,Hsin-Meng Liu,Ming-Chung Deng,Paul Becher,Yu-Chun Huang,Nicholas Berkley,Fun-In Wang,Kuo-Jung Tsai

doi:10.3390/v13081655

Abstract

Classical swine fever virus (CSFV) shares high structural and antigenic homology with bovine viral diarrhea virus (BVDV) and border disease virus (BDV). Because all three viruses can infect swine and elicit cross-reactive antibodies, it is necessary to differentiate among them with regard to serological diagnosis of classical swine fever. To understand the mechanism of cross-reactivity, it is important to define common or specific epitopes of these viruses. For this purpose, epitope mapping of six monoclonal antibodies (mAbs) was performed using recombinant expressed antigenic domains of CSFV and BDV E2 proteins. One CSFV-specific conformational epitope and one CSFV and BDV common epitope within domain B/C of E2 were identified. Site-directed mutagenesis confirmed that residues G725 and V738/I738 of the CSFV-specific epitope and P709/L709 and E713 of the second epitope are important for mAbs binding. Infection of CSFV in porcine cells was significantly reduced after pre-incubation of the cells with the domain B/C of E2 or after pre-incubation of CSFV with the mAbs detecting domain B/C. 3D structural modeling suggested that both epitopes are exposed on the surface of E2. Based on this, the identified epitopes represent a potential target for virus neutralization and might be involved in the early steps of CSFV infection.

Highlights

We demonstrate the presence of a Classical swine fever virus (CSFV)-specific conformational epitope and a CSFV and border disease virus (BDV) common conformational epitope within the domain B/C of glycoprotein E2
The monoclonal antibodies (mAbs) 3C1E12 clearly detected all CSFV and BDV genotypes, except for the CSFV genotype 1.1 strains, which reacted weakly, with only 2–4 cells staining positive, and resulted in negative staining with CSFV genotype 3.1
The mAb WH304 represents the only antibody of the current study that is CSFV specific independently of the CSFV genotype

Summary

Introduction

Classical swine fever virus (CSFV; Pestivirus C) is the etiological agent of classical swine fever (CSF), which is a highly contagious disease of swine. CSFV is an enveloped positivestranded RNA virus, which together with bovine viral diarrhea virus (BVDV) type-1. CSFV infection is limited to swine, while BVDV and BDV infect both ruminants and swine. Infections of swine with ruminant pestiviruses can result in the production of cross-reacting antibodies, which can cause problems within the serological diagnosis of CSF [5]. It has been described that the Aydin pesitivirus and the novel ovine pestivirus from Italy are more closely related to CSFV than to BDV, resulting in significant interference with the serological diagnosis of CSF [8,9,10,11]

Methods

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Discussion

Conclusion