Genetic resistance - an alternative for controlling PRRS?

Abstract

PRRS is one of the most challenging diseases for world-wide pig production. Attempts for a sustainable control of this scourge by vaccination have not yet fully satisfied. With an increasing knowledge and methodology in disease resistance, a new world-wide endeavour has been started to support the combat of animal diseases, based on the existence of valuable gene variants with regard to any host-pathogen interaction. Several groups have produced a wealth of evidence for natural variability in resistance/susceptibility to PRRS in our commercial breeding lines. However, up to now, exploiting existing variation has failed because of the difficulty to detect the carriers of favourable and unfavourable alleles, especially with regard to such complex polygenic traits like resistance to PRRS. New hope comes from new genomic tools like next generation sequencing which have become extremely fast and low priced. Thus, research is booming world-wide and the jigsaw puzzle is filling up – slowly but steadily. On the other hand, knowledge from virological and biomedical basic research has opened the way for an “intervening way”, i.e. the modification of identified key genes that occupy key positions in PRRS pathogenesis, like CD163. CD163 was identified as the striking receptor in PRRSV entry and its knockout from the genome by gene editing has led to the production of pigs that were completely resistant to PRRSV – a milestone in modern pig breeding. However, at this early step, concerns remain about the acceptance of societies for gene edited products and regulation still awaits upgrading to the new technology. Further questions arise with regard to upcoming patents from an ethical and legal point of view. Eventually, the importance of CD163 for homeostasis, defence and immunity demands for more insight before its complete or partial silencing can be answered. Whatever path will be followed, even a partial abolishment of PRRSV replication will lead to a significant improvement of the disastrous herd situation, with a significant impact on welfare, performance, antimicrobial consumption and consumer protection. Genetics will be part of a future solution.

The ethics of genome editing in non-human animals: a systematic review of reasons reported in the academic literature

“…It was mentioned that CRISPR could be relatively inexpensive in comparison to both previous genetic technologies [9,26,34,110,114,132,142], other pest management techniques such as insecticides [20,23] and traditional sterile insect methods [23], and that it could increase economic productivity in animals bred for human consumption [97,137]. Moreover, authors mentioned that genome editing could save costs for the farming industry by providing animals with disease resistance [70,75,86,98,126] or by transferring polled genes to horned cattle, obviating the need for expensive dehorning [19,79,87,96]. Finally, gene drives could be a cost-effective strategy for controlling the transmission of vector-borne diseases [6,27,109].…”

“…Other authors emphasized the potential use of genome editing to increase animal health and welfare by making animals resistant to diseases [78,80,96,98,126,133,135,139] or better able to adapt to environmental conditions [19,137]. By contrast, it was argued that such uses of genome editing would enable even greater intensification of farming, for example, by generating polled or disease resistant animals that could be kept at higher density [36,104,116].…”

“…could be more efficient, versatile, precise, easy to use or accurate than previous editing technologies 39 [3,4,6,7,9,33 - could be a cost-effective strategy to control the transmission of vector-borne diseases 3 [6,27,102] genetic modification, gene drives could increase economic productivity in animals bred for human consumption 2 [97,137] various (ZFNs, TALEN, CRISPR); genetic engineering could provide animals with disease resistance, which could reduce the overuse of antibiotics 2 [98,139] various (TALEN, CRISPR) could be used to eradicate vector-borne diseases in a more efficacious and/or logistically less complex way than other efforts to eliminate these diseases 2 [27,28] gene drives could be used for pest control, being more precise or effective than other pest management methods such as pesticides 2 [20,109] gene drives re the possibility of off-target effects: these are fewer and more controlled compared with the mutations that are caused by generally accepted technologies such as conventional breeding 2 [80,142] various (ZFNs, TALEN, CRISPR) re the possibility of off-target effects: these can be minimized by careful design and testing, and their effects are largely identical to those of the natural processes that continually create variation in the genomes of food animals 1 [85] various (ZFNs, TALEN, CRISPR)…”

“…could decrease animal suffering in dairy farming by creating dehorned cattle, preventing invasive and painful dehorning 10 [9,19,78 -80,85,96,126,139,140] various (ZFNs, TALEN, CRISPR) could counter welfare problems by creating the so-called diminished animals in which the ability to sense pain is impaired 8 [78,112,115,116,[119][120][121]137] genome editing (CRISPR); genetic engineering/modification could increase animal health and welfare by providing animals with disease resistance 8 [78,80,96,98,126,133,135,139] [19,137] various (ZFNs, TALEN, CRISPR); genetic engineering could be used to prevent the killing of day-old male chicks 2 [100,126] CRISPR; genetic modification re the possible creation of animals with welfare problems: if they have a life worth living we cannot say that they are worse off owing to the genetic modification, for if they had not been created with genetic modification, they would not have existed at all 2 [115,118] genetic modification re off-target effects: could result in fewer off-target effects than previous techniques, which could improve welfare of genetically modified animals 1 [9] CRISPR could reduce the numbers of animals used to create model organisms compared to traditional methods, which typically sacrifice many animals before achieving the desired genotype and phenotype 1 [110] CRISPR could remove known harmful recessive alleles that impair fertility or health and in that sense repair accumulated damage in the genome of breeding animals 1 [96] various (ZFNs, TALEN, CRISPR) could prevent wild animal suffering by using genome editing to change reproductive behaviour; the harm that would be prevented by doing so would outweigh the harm of developing and testing these strategies 1 [114] CRISPR could lead us to ignore the predicament of the animal and to accept negative effects on animal welfare for the sake of other goals; however, this concern may be addressed by using less drastic gene drive designs and using these to promote animal welfare 1…”

Invited review: Piglet survival: benefits of the immunocompetence

“…Promising genetic resistance against the porcine reproductive and respiratory syndrome (PRRS) was reviewed by Reiner (2016) and Dekkers et al (2017). However, Dekkers et al (2017) stress that due to the variability of PRRS a resistance is not feasible, but a reduced susceptibility is.…”