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Segalés: PCV2 and control measures continue to evolve

16 February 2021, at 11:36am

“Porcine circovirus type 2 systemic disease (PCV2-SD) was a devastating disease before vaccines,” said Joaquim Segalés, DVM, PhD, professor in the Department of Animal Health and Anatomy at the Universitat Autònoma de Barcelona, Spain. “It wasn’t just mortality ⸺ it was the number of runts and pigs with lower weight gain. Vaccination was a huge added value for producers because more animals reached a proper slaughter weight. Even antibiotic expenses diminished significantly because PCV2-SD is an immunosuppressive disease. We have never been able to demonstrate real vaccine failure in the cases with which I’m familiar. Vaccination failure is another issue, which may be related to lack of proper conservation, application or timing of such application.”

Joaquim Segalés, DVM, PhD
Joaquim Segalés, DVM, PhD

A member of the family Circoviridae, PCV2 is considered one of the most economically important viral agents in swine worldwide.1 A single-strand DNA virus, PCV2 has a mutation rate that is relatively high, sometimes comparable to RNA viruses like retroviruses, Segalés said. It is unique from other porcine circoviruses because both PCV1 and PCV3 have lower mutation rates.2 PCV2 is closely associated with postweaning multisystemic wasting syndrome,3 which the disease was initially called. The most important clinical signs are emaciation and growth retardation; however, respiratory or digestive problems can be present. More importantly, lesions seen through histopathology are of concern, since lymphocyte depletion and granulomatous inflammation of lymphoid tissues are the hallmarks of the disease.

Over time, the virus has changed, but most changes due to mutation are “silent,” meaning the amino acid associated with that particular nucleotide doesn’t change, Segalés said. Differences in antigenicity are evident when certain monoclonal antibodies are used, but when dealing with a polyclonal response, major differences are not apparent.

Change from a 4- to 8-genotype classification

From the beginning, researchers recognized that PCV2 had two, clearly different clusters.4

“Research groups from all over the world started talking about two potential genotypes, but it was confusing because some people used, ‘Genotype 1, Genotype 2,’ while others used ‘A’ and ‘B,’” said Segalés, who also served as director of the Animal Health Research Center at the Institute of Agrifood Research and Technology between 2012 and 2017. “Thanks to a 2008 European project led by Gordon Allan, PhD, the first genotype definition was proposed, in which the existence of two major genotypes, A and B, was proposed to the international community.”5

When there was at least a 3.5% difference in the genome, a new genotype could be considered, he added. Over time, the number of sequences grew, and eventually, that separation was not efficient.

PCV2 genotype c was discovered retrospectively in Denmark in the 1980s and has been detected in other countries,6 Segalés said. Then, PCV2d, a mutant form of PCV2b, came along.

“In 2018, Dr. Giovanni Franzo at the University of Padua (Italy) and I developed a better way of distinguishing between genotypes,”7 he said. “From a practical standpoint, we were able to establish eight different genotypes (a, b, c, d, e, f, g and h), although within the genotypes listed, some are poorly represented. Most sequences now are from PCV2d, followed by PCV2b and PCV2a. The rest of the genotypes are in the minority.”

Present PCV2 status around the world

Most genotypes exist in the worldwide pig population, likely due to global trade, Segalés said.
“Studies performed 10 years ago clearly demonstrated how different genotypes were traveling around the world,” he noted. “PCV2d is the most prevalent circovirus now. It was detected first in China, then in North America and, most recently, Europe. We have been able to find PCV2a, b and d in different European countries, and it’s very likely that all viruses from three major genotypes are still circulating. Prevalence may reflect the timing in which those sequences were identified, so we have to be careful about the interpretation of adjusting sequences.”

PCV2d is followed relatively closely by PCV2b and, at more distance, PCV2a, in terms of prevalence, though Segalés said this doesn’t mean other genotypes are not circulating. “It does, however, mean other genotypes don’t have the same representation and geographical distribution as the other three,” he said.

Other genotypes may appear in the future, Segalés said, but as long as those genotypes are not mutant escapes from the immunity provided by the vaccine, they are not necessarily relevant for the veterinary community.

“The vaccines really work well,” he stressed. “By the year 2000, we saw a change in genotype prevalence from a to b, and this coincided with a huge spread of severe disease throughout the world because there were no vaccines at that time. By the mid-2010 decade there was another change in prevalence to PCV2d instead of PCV2b, but reasons for the new genotype shift are not really clear to us.

“PCV2 is a species for scientific purposes, just like PCV1, PCV3 and now, PCV4,” Segalés continued. “There are no classifications below the species level by the International Committee for Taxonomy of Viruses. If the antigenicity and the protection doesn’t change much, it shouldn’t be a major problem. But taking into account that this virus changes over time and has a high mutation rate, maintaining a surveillance system is important.”

PCV2 recombination potential

The virus might undergo recombination in a relatively easy manner, Segalés said.

“However, recombination events imply infection of the same cell with two different viruses, and if we’re talking about recombination, we are mostly thinking in terms of different genotypes,” he explained. “We have detected recombinants among nearly all the major PCV2 genotypes existing so far. Taking into account the cross-protection between the genotypes, recombination isn’t a major factor to date, since we have only one single protein. In other words, recombination doesn’t seem to affect vaccine efficacy.

“What we do not have are side-by-side study comparisons regarding the efficacy of existing vaccines and their effect on all the genotypes,” he added. “In fact, to perform a comparative experiment would be extremely expensive. However, slight differences are almost impossible to identify. The common knowledge is that vaccines are able to control the circulating genotypes.”

Management of PCV2

There is a small proportion of cases that may not be getting the efficiency value they expect, or they may see overt disease in spite of vaccination, Segalés said.

“Those particular cases need practical research because they may have a subpopulation issue,” he said. “The problem is likely not the vaccine but, rather, a change in the epidemiology of the virus. In these cases, we must investigate and monitor the infection. We will need to get the serology/PCR to identify what’s going on and determine where the infection is taking place. We must remember that the end result of systemic disease is multifactorial disease, and there are a number of issues to investigate.”

Before changing anything, the producer and veterinarian must establish a proper diagnosis of the condition on the farm, Segalés recommended. This includes looking at seasonality, facilities and animal flows as well as potential infectious agents. This is a key message in all cases because even when vaccines are effective, good management is essential in well-run operations.

“This is an ever-changing virus so you never know what will happen in the future. But we know this virus was already in the pig population in the 1960s, and although we’ve had PCV2 vaccines for slightly more than a decade, we are still happy with the protection offered,” Segalés said.

“There’s a typical saying we use here in Spain: If something works, don’t touch it,” he concluded. “In other words, there is no need to change anything regarding vaccination against PCV2 if there is no evidence for it.”

References
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1 Saporiti V, Huerta E, Correa-Fiz F, Grosse Liesner B, Duran O, Segalés J, Sibila M. Detection and genotyping of Porcine circovirus 2 (PCV-2) and detection of Porcine circovirus 3 (PCV-3) in sera from fattening pigs of different European countries. https://pubmed.ncbi.nlm.nih.gov/32356364/ Accessed Nov. 6, 2020.
2 Yee Tan C, Opaskornkul K, Thanawongnuwech R, Hassan L, Toung Ooi P. First molecular detection and complete sequence analysis of porcine circovirus type 3 (PCV3) in Peninsular Malaysia. 2020 July 24. https://doi.org/10.1371/journal.pone.0235832
3 Khaiseb S, Sydler T, Zimmermann D, Pospischil A, Sidler X, Brugnera E. Coreplication of the Major Genotype Group Members of Porcine Circovirus Type 2 as a Prerequisite to Coevolution May Explain the Variable Disease Manifestations. J Virol. 2011 Nov;85(21):11111-11120 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3194933/ Accessed Nov. 6, 2020.
4 Olvera A, Cortey M, Segales J. Molecular evolution of porcine circovirus type 2 genomes: Phylogeny and clonality. https://doi.org/10.1016/j.virol.2006.07.047 Accessed Nov. 6, 2020.
5 Timmusk S, Wallgren P, Brunborg I, Wikstrom F, Allen G, Meehan B, McMenamy M, McNeilly F, Fuxler L, Belak K, Podersoo D, Saar T, Berg M, Fossum C. Phylogenetic analysis of porcine circovirus type 2 (PCV2) pre- and post-epizootic postweaning multisystemic wasting syndrome (PMWS). Vet Microbiol. 2008 June 1. https://www.sciencedirect.com/science/article/pii/S0378113507004749 Accessed Nov. 6, 2020.
6 Dupont K, Nielsen EO, Bækbo P, Larsen LE. Genomic analysis of PCV2 isolates from Danish archives and a current PMWS case-control study supports a shift in genotypes with time. Vet Microbiol. 2008;128:56-64. 10.1016/j.vetmic.2007.09.016
7 Franzo G, Segales, J. Porcine circovirus 2 (PCV-2) genotype update and proposal of a new genotyping methodology. 2018 Dec. https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208585 Accessed Nov. 6, 2020.

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