Viral meningitis epidemics and a single, recent, recombinant and anthroponotic origin of swine vesicular disease virus

Background and objectives: 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. Methodology: 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. Results: 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. Conclusions and implications: 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.