OMIA 001752-9823 : Resistance to porcine reproductive and respiratory syndrome (PRRS) virus in Sus scrofa

Mendelian trait/disorder: no

Mode of inheritance: Multifactorial

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2018

Species-specific description: The pigs developed by Wells et al. (2016) and other papers included in the reference list are genetically-modified organisms (GMO)

Markers: Boddicker et al. (2012) reported a single large-effect QTL in a 1Mb region of chromosome SSC4. Boddicker et al. (2013) confirmed this effect in two independent populations.

Molecular basis: Noting that there appears to be no biological function of the SRCR5 scavenger receptor cysteine-rich domain of the CD163 peptide, apart from being essential for infection by the PRRS virus (PPRSV), Burkard et al. (2017) "generated pigs lacking SRCR5 [ΔSRCR5 pigs] by the deletion of exon 7 of CD163 using CRISPR/Cas9 editing and showed that macrophages from these pigs were resistant to both PRRSV-1 and PRRSV-2 infection in vitro". As an in vivo follow-up, Burkhard et al. (2018) showed that "ΔSRCR5 pigs are fully resistant to infection by the virus", demonstrating "that a genetic-control approach results in complete resistance to PRRSV infection in vivo. CD163 is edited so as to remove the viral interaction domain while maintaining protein expression and biological function, averting any potential adverse effect associated with protein knockout."

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
CD163 CD163 molecule Sus scrofa 5 NC_010447.5 (63300200..63334497) CD163 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Resistance to PRRS virus CD163 deletion, gross (>20) Burkhard et al (2018): "the deletion of exon 7 of CD163 using CRISPR/Cas9 editing" 2018 29925651

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2018 Burkard, C., Opriessnig, T., Mileham, A.J., Stadejek, T., Ait-Ali, T., Lillico, S.G., Whitelaw, C.B.A., Archibald, A.L. :
Pigs Lacking the Scavenger Receptor Cysteine-Rich Domain 5 of CD163 Are Resistant to Porcine Reproductive and Respiratory Syndrome Virus 1 Infection. J Virol 92:, 2018. Pubmed reference: 29925651. DOI: 10.1128/JVI.00415-18.
Yang, H., Zhang, J., Zhang, X., Shi, J., Pan, Y., Zhou, R., Li, G., Li, Z., Cai, G., Wu, Z. :
CD163 knockout pigs are fully resistant to highly pathogenic porcine reproductive and respiratory syndrome virus. Antiviral Res 151:63-70, 2018. Pubmed reference: 29337166. DOI: 10.1016/j.antiviral.2018.01.004.
2017 Burkard, C., Lillico, S.G., Reid, E., Jackson, B., Mileham, A.J., Ait-Ali, T., Whitelaw, C.B., Archibald, A.L. :
Precision engineering for PRRSV resistance in pigs: Macrophages from genome edited pigs lacking CD163 SRCR5 domain are fully resistant to both PRRSV genotypes while maintaining biological function. PLoS Pathog 13:e1006206, 2017. Pubmed reference: 28231264. DOI: 10.1371/journal.ppat.1006206.
Wells, K.D., Bardot, R., Whitworth, K.M., Trible, B.R., Fang, Y., Mileham, A., Kerrigan, M.A., Samuel, M.S., Prather, R.S., Rowland, R.R. :
Replacement of Porcine CD163 Scavenger Receptor Cysteine-Rich Domain 5 with a CD163-Like Homolog Confers Resistance of Pigs to Genotype 1 but Not Genotype 2 Porcine Reproductive and Respiratory Syndrome Virus. J Virol 91:, 2017. Pubmed reference: 27847356. DOI: 10.1128/JVI.01521-16.
2016 Whitworth, K.M., Rowland, R.R., Ewen, C.L., Trible, B.R., Kerrigan, M.A., Cino-Ozuna, A.G., Samuel, M.S., Lightner, J.E., McLaren, D.G., Mileham, A.J., Wells, K.D., Prather, R.S. :
Gene-edited pigs are protected from porcine reproductive and respiratory syndrome virus. Nat Biotechnol 34:20-2, 2016. Pubmed reference: 26641533. DOI: 10.1038/nbt.3434.
2014 Boddicker, N.J., Garrick, D.J., Rowland, R.R., Lunney, J.K., Reecy, J.M., Dekkers, J.C. :
Validation and further characterization of a major quantitative trait locus associated with host response to experimental infection with porcine reproductive and respiratory syndrome virus. Anim Genet 45:48-58, 2014. Pubmed reference: 23914972. DOI: 10.1111/age.12079.
2013 Wang, D., Cao, L., Xu, Z., Fang, L., Zhong, Y., Chen, Q., Luo, R., Chen, H., Li, K., Xiao, S. :
MiR-125b reduces porcine reproductive and respiratory syndrome virus replication by negatively regulating the NF-κB pathway. PLoS One 8:e55838, 2013. Pubmed reference: 23409058. DOI: 10.1371/journal.pone.0055838.
2012 Boddicker, N., Waide, E.H., Rowland, R.R., Lunney, J.K., Garrick, D.J., Reecy, J.M., Dekkers, J.C. :
Evidence for a major QTL associated with host response to porcine reproductive and respiratory syndrome virus challenge. J Anim Sci 90:1733-46, 2012. Pubmed reference: 22205662. DOI: 10.2527/jas.2011-4464.
2010 Van Gorp, H., Van Breedam, W., Van Doorsselaere, J., Delputte, P.L., Nauwynck, H.J. :
Identification of the CD163 protein domains involved in infection of the porcine reproductive and respiratory syndrome virus. J Virol 84:3101-5, 2010. Pubmed reference: 20032174. DOI: 10.1128/JVI.02093-09.

Edit History


  • Created by Frank Nicholas on 26 Nov 2012
  • Changed by Frank Nicholas on 12 Aug 2013
  • Changed by Frank Nicholas on 22 Nov 2016
  • Changed by Frank Nicholas on 21 Aug 2018