A Shift in Porcine Circovirus 3 (PCV-3) History Paradigm: Phylodynamic Analyses Reveal an Ancient Origin and Prolonged Undetected Circulation in the Worldwide Swine Population

The identification of a new circovirus (Porcine circovirus 3, PCV-3) has raised a remarkable concern because of some analogies with Porcine circovirus 2 (PCV-2). Preliminary results suggest an extremely recent PCV-3 emergence and high mutation rate. Retrospective studies prove its circulation at least since the early 1990s, revealing that PCV-3 could have been infecting pigs for an even longer period. Therefore, a new evaluation, based on an updated collection of PCV-3 sequences spanning more than 20 years, is performed using a phylodynamic approach. The obtained results overrule the previous PCV-3 history concept, indicating an ancient origin. These evidences are associated with an evolutionary rate far lower (10(-5)-10(-6) substitution/site/year) than the PCV-2 one. Accordingly, the action of selective pressures on PCV-3 open reading frames (ORFs) seems to be remarkably lower compared to those acting on PCV-2, suggesting either a reduced PCV-3 plasticity or a less efficient host-induced natural selection. A complex and not-directional viral flow network is evidenced through phylogeographic analysis, indicating a long lasting circulation rather than a recent emergence followed by spreading. Being recent emergence has been ruled out, efforts should be devoted to understand whether its recent discovery is simply due to improved detection capabilities or to the breaking of a previous equilibrium.