Porcine circovirus 2 (PCV2) emerged as a clinical issue presenting as Post-Weaning Multisystemic Wasting Syndrome (PMWS) in some isolated regions during the 1990’s. Although most DNA viruses have a reputation of being more genetically stable than their RNA cousins the PCV2 virus exhibits a relatively high evolutionary potential due to both high mutation and recombination rates. Consequently, different genotypes including PCV2a , b, c, d, e, f, g, h, i have emerged over time. It is now thought that PCV2a has been kicking around since the early 20th century. PCV2a was eventually displaced as the dominant genotype by PCV2b around 2000 to 2003. Finally PCV2d became the predominant genotype starting around 2010 to 2014 depending on region. While PCV2d was initially considered a PCV2b-mutant it appears that it is more probable that PCV2d originated along similar timelines as PCV2b but it’s peak at a later time is speculated to be linked to the widespread application of PCV2a-based vaccines. Although PCV2d is currently the most common genotype the other genotypes continue to circulate.
These European researchers wanted to look at the epidemiological and evolutionary patterns of PCV2 genotypes using phylodynamic analyses. Some 8,283 sequences from around the globe were included in the final dataset and this constitutes an almost 10-fold increase in ORF2 sequence availability when compared to previous epidemiological studies. Because the sequences were categorized by region, the phylogeographic analysis was able to shed light on viral dispersal patterns and frequency. Selective pressures acting on the capsid protein (immune recognition) were estimated and compared among genotypes. PCV2 “clades” from different continents were interspersed throughout the phylogenetic tree and this indicated that frequent strain exchanges occurred between different regions of the world and that after establishment of a new strain within a region the future virus evolution was independent within that new location. Some very small clades did end up as “epidemiological dead ends”.
The researchers provided the following interpretations of the study findings:
- While successive emergence of major genotypes was confirmed, this study extends previous findings by revealing subsequent prevalence fluctuations of PCV2a and PCV2b after their initial decline. This evolutionary process may represent an example of balancing selection, specifically negative frequency-dependent selection, where a genotype fitness diminishes as it becomes more common, and vice versa. Negative frequency -dependent selection selects for the more “rare” genotypes in a population and this results in an increase of the population’s genetic variance because the minor genotypes tend to not completely die out and can re-emerge.
- Variations in genotype specific immunity of the host combined with the periodic introduction of strains that have independently evolved in different regions may have led to fluctuations in the population dynamics of major genotypes over time. These fluctuations were associated with ongoing evolution and variations in the capsid amino acid profile.(immune generating viral bits)
Take Home Messages:
- The researchers commented that so far the scientific evidence shows that using a vaccine prepared with one genotype will provide remarkably good cross-protection for all the genotypes. The researchers commented that most cases of so-called “vaccine failure” are usually attributable to improper vaccination management. Is the cross-protection perfect? Well , not quite perfect given that there are slightly higher levels of viremia and slightly lower levels of virus neutralizing antibodies for heterologous challenge. (Vaccine and attacking strain not the same). While not clinically significant, even a marginal differential in cross-protection, when acting on very very large viral populations, could facilitate some sort of the negative frequency-dependent selection that helps keep most of the genotypes hanging around in the background while one genotype emerges to be predominant.
- The researchers went on to say that the multifactorial nature of PCVDs suggests that a combination of viral, host and environmental factors including co-infections, nutrition, management, animal movements, biosecurity, control strategies, and other factors are all likely to be involved in selective pressure for genetic change.
- We are blessed to have such effective vaccines for PCVD. (If only we could be so lucky with PRRS vaccines) Having indicated that, the researchers said that it is still worthy to aspire to perfect the cross-protection of PCVD vaccines in order to diminish the opportunities for negative frequency genetic selection that can shift the genotype landscape.
References: Giovanni Franzo , Claudia Maria Tucciarone , Matteo Legnardi , Michele Drigo , Joaquim Segalés An updated phylogeography and population dynamics of porcine circovirus 2 genotypes: are they reaching an equilibrium? Front Microbiol . 2024 Oct 29:15:1500498. doi: 10.3389/fmicb.2024.1500498. eCollection 2024.
