Abstract

Swine vesicular disease virus (SVDV) is a close relative of the human Enterovirus B serotype, coxsackievirus B5. As the etiological agent of a significant emergent veterinary disease, several studies have attempted to explain its origin. However, several key questions remain, including the full biological ancestry of the virus, and its geographical and temporal origin. We sequenced near-complete genomes of 27 SVDV and 13 coxsackievirus B5 samples, all originally isolated between 1966 and 2006, and analysed these in conjunction with existing sequences and historical information. While analyses incorporating 24 additional near-complete SVDV genomic sequences indicate clear signs of within-SVDV recombination, all 51 SVDV isolates remain monophyletic. This supports a hypothesis of a single anthroponotic transfer origin. Analysis of individual coding and non-coding regions supports that SVDV has a recombinant origin between coxsackievirus B5 and another Enterovirus B serotype, most likely coxsackievirus A9. Extensive Bayesian sequence-based analysis of the time of the most recent common ancestor of all analysed sequences places this within a few years around 1961. Epidemiological evidence points to China as an origin, but there are no available samples to test this conclusively. Historical investigation and the clinical aspects of the involved Enterovirus B serotypes, makes the current results consistent with a hypothesis stating that SVDV originated through co-infection, recombination, and a single anthroponotic event, during large viral meningitis epidemics around 1960/1961 involving the ancestral serotypes. The exact geographical origin of SVDV may remain untestable due to historical aspects.

Highlights

  • Swine vesicular disease virus (SVDV) is the etiological agent of swine vesicular disease (SVD) [1,2]

  • 26 SVDV and 13 coxsackievirus B5 (CV-B5) isolates grown in a pig kidney cell line (IB-RS-2) were selected for near-complete genome sequencing on the Illumina HiSeq platform, an additional SVDV isolate (HKN/19/70) was sequenced subsequently on the Illumina MiSeq platform, for a total of 27 SVDV isolates (Table 1 and Supplementary Table S4, for an overview of isolates included in this study)

  • Within-SVDV recombination analysis was conducted to ascertain which genomic regions were free of recombination signals, and suitable for use in the Bayesian dating estimates analyses

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Summary

Introduction

Swine vesicular disease virus (SVDV) is the etiological agent of swine vesicular disease (SVD) [1,2]. A pathogen of swine, previous studies have noted close similarity in the capsid region to another Enterovirus B serotype, coxsackievirus B5 (CV-B5)—an observation that is notable due to its status as a human pathogen linked to a range of cardiovascular and neurological pathologies [4,5,6,7] Given this tantalising link, and in particular the suggestion that SVDV may have originated as an anthroponotic transfer (i.e. human to swine), several studies have previously attempted to identify the geographical, temporal, and biological origin of SVDV [7,8].

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