Phylodynamics of classical swine fever virus with emphasis on Ecuadorian strains

Classic swine fever virus (CSFV) is a Pestivirus from the Flaviviridae family that affects pigs worldwide and is endemic in several Latin American countries. However, there are still some countries in the region, including Ecuador, for which CSFV molecular information is lacking. To better understand the epidemiology of CSFV in the Americas, sequences from CSFVs from Ecuador were generated and a phylodynamic analysis of the virus was performed. Sequences for the full-length glycoprotein E2 gene of twenty field isolates were obtained and, along with sequences from strains previously described in the Americas and from the most representative strains worldwide, were used to analyse the phylodynamics of the virus. Bayesian methods were used to test several molecular clock and demographic models. A calibrated ultrametric tree and a Bayesian skyline were constructed, and codons associated with positive selection involving immune scape were detected. The best model according to Bayes factors was the strict molecular clock and Bayesian skyline model, which shows that CSFV has an evolution rate of 3.2x10(-4) substitutions per site per year. The model estimates the origin of CSFV in the mid-1500s. There is a strong spatial structure for CSFV in the Americas, indicating that the virus is moving mainly through neighbouring countries. The genetic diversity of CSFV has increased constantly since its appearance, with a slight decrease in mid-twentieth century, which coincides, with eradication campaigns in North America. Even though there is no evidence of strong directional evolution of the E2 gene in CSFV, codons 713, 761, 762 and 975 appear to be selected positively and could be related to virulence or pathogenesis. These results reveal how CSFV has spread and evolved since it first appeared in the Americas and provide important information for attaining the goal of eradication of this virus in Latin America.