Phylodynamic analysis of current Porcine circovirus 4 sequences: Does the porcine circoviruses evolutionary history repeat itself?

Four porcine circoviruses (PCVs) have been discovered over time and seem to share a common history, particularly for PCV-2 and -3. Despite being reported as apparently new viruses, rapidly emerging as a threat for the worldwide swine industry, they were then proven to have been circulating and coexisting with domestic pigs undetected for decades, without causing relevant health issues. A similar scenario could be true for the most recently identified PCV-4. However, its detection in Asia only and the limited genetic variability could suggest a truly recent origin. To investigate which of the above-mentioned scenarios is more plausible, a phylodynamic analysis was performed on all available PCV-4 sequences for which adequate metadata were available to reconstruct the viral history and evolution. Obtained results suggest an ancient origin, at least decades ago, followed by a prolonged low-level circulation and a moderate increase in viral population size after the second half of the XX century, in parallel with a progressive rise in pig population and farming intensification. A relevant local geographical clustering was also highlighted. The reason behind such low spreading capacity and limited geographical distribution compared to other circoviruses is currently obscure and will require dedicated studies, involving a more extensive sampling and sequencing activity.