OMIA:001752-9823 : Resistance/susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) in Sus scrofa (pig) |
Categories: Immune system phene
Links to possible relevant human trait(s) and/or gene(s) in OMIM: 613646 (trait) , 605545 (gene)
Mendelian trait/disorder: no
Mode of inheritance: Multifactorial
Disease-related: 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." Wang et al. (2019) "generated CD163 exon 7 deleted (CD163E7D) pigs using CRISPR/Cas9 mediated homologous recombination and somatic cell nuclear transfer (SCNT). The deletion of exon 7 had no adverse effects on CD163-associated functions. Pigs were further challenged with a highly pathogenic PRRSV (HP-PRRSV) strain. The CD163E7D pigs exhibited mild clinical symptoms and had decreased viral loads in blood. All CD163E7D pigs survived the viral challenge, while all the WT pigs displayed severe symptoms, and 2 out of 6 WT pigs died during the challenge. Our results demonstrated that CD163 exon 7 deletion confers resistance to HP-PRRSV infection without impairing the biological functions of CD163." Salgado et al. (2024) "produced pigs [via genome editing] possessing a defined CD163 exon 13 deletion (ΔExon13 pigs) and evaluated their susceptibility to viral infection. Wild type (WT) and CD163 modified pigs, placed in the same room, were infected with PRRSV-2. The modified pigs remained PCR and serologically negative for PRRSV throughout the study; whereas the WT pigs supported PRRSV infection and showed PRRSV related pathology."
Ren et al. (2024) “generated porcine fibroblasts with simultaneous knockouts of IGF2, ANPEP, CD163, and MSTN via Cas12iMax in one step. Phenotypically stable pigs were created through somatic cell nuclear transfer technology. They exhibited improved growth performance and muscle quality.” This study involves genetically modified organisms (GMO)
Genetic engineering:
Yes - in addition to the occurrence of natural variants, variants have been created artificially, e.g. by genetic engineering or gene editing
Have human generated variants been created, e.g. through genetic engineering and gene editing
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
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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.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
| OMIA Variant ID | Breed(s) | Variant Phenotype | Gene | Allele | Type of Variant | Source of Genetic Variant | Reference Sequence | Chr. | g. or m. | c. or n. | p. | Verbal Description | EVA ID | Year Published | PubMed ID(s) | Acknowledgements |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1008 | Resistance to PRRS virus | CD163 | deletion, gross (>20) | Naturally occurring variant | 5 | Burkhard et al (2018): "the deletion of exon 7 of CD163 using CRISPR/Cas9 editing" | 2018 | 29925651 |
Cite this entry
Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:001752-9823: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70
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.
| 2024 | [No authors listed] : |
| Correction to: Generation of a commercial-scale founder population of porcine reproductive and respiratory syndrome virus resistant pigs using CRISPR-Cas by Burger et al. The CRISPR Journal, 2023;7(1):12-28; DOI: 10.1089/crispr.2023.0061. CRISPR J 7:131, 2024. Pubmed reference: 38635331. DOI: 10.1089/crispr.2023.0061.correx. | |
| Burger, B.T., Beaton, B.P., Campbell, M.A., Brett, B.T., Rohrer, M.S., Plummer, S., Barnes, D., Jiang, K., Naswa, S., Lange, J., Ott, A., Alger, E., Rincon, G., Rounsley, S., Betthauser, J., Mtango, N.R., Benne, J.A., Hammerand, J., Durfee, C.J., Rotolo, M.L., Cameron, P., Lied, A.M., Irby, M.J., Nyer, D.B., Fuller, C.K., Gradia, S., Kanner, S.B., Park, K.E., Waters, J., Simpson, S., Telugu, B.P., Salgado, B.C., Brandariz-Nuñez, A., Rowland, R.R.R., Culbertson, M., Rice, E., Cigan, A.M. : | |
| Generation of a commercial-scale founder population of porcine reproductive and respiratory syndrome virus resistant pigs using CRISPR-Cas. CRISPR J 7:12-28, 2024. Pubmed reference: 38353617. DOI: 10.1089/crispr.2023.0061. | |
| Fraile, L., Vidal, A., Romero, J., Abella, G., Gracia, J., Blanco-Penedo, I., Pena, R.N. : | |
| Validation of a phenotyping method to identify PRRSV-resilient sows and its impact on sow stayability. J Anim Sci :skae232, 2024. Pubmed reference: 39132682. DOI: 10.1093/jas/skae232. | |
| Ko, H., Pasternak, J.A., Mulligan, M.K., Hamonic, G., Ramesh, N., MacPhee, D.J., Plastow, G.S., Harding, J.C.S. : | |
| A DIO2 missense mutation and its impact on fetal response to PRRSV infection. BMC Vet Res 20:255, 2024. Pubmed reference: 38867209. DOI: 10.1186/s12917-024-04099-4. | |
| Laghouaouta, H., Fraile, L.J., Estany, J., Pena, R.N. : | |
| Candidate markers for enhanced host response to PRRS have scarce adverse effects on pigs' growth and production. Porcine Health Manag 10:29, 2024. Pubmed reference: 39169441. DOI: 10.1186/s40813-024-00379-5. | |
| Liu, Y., Yang, L., Xiang, H.Y., Niu, M., Deng, J.C., Li, X.Y., Hao, W.J., Ou-Yang, H.S., Liu, T.Y., Tang, X.C., Pang, D.X., Yuan, H.M. : | |
| Genetically modified pigs with CD163 point mutation are resistant to HP-PRRSV infection. Zool Res 45:2095-8137(2024)04-0833-12:833-844, 2024. Pubmed reference: 39004861. DOI: 10.24272/j.issn.2095-8137.2024.090. | |
| Mills, G. : | |
| Creating PRRS-resistant pigs for the supermarket. Vet Rec 194:214-215, 2024. Pubmed reference: 38488584. DOI: 10.1002/vetr.4057. | |
| Nesbitt, C., Galina Pantoja, L., Beaton, B., Chen, C.Y., Culbertson, M., Harms, P., Holl, J., Sosnicki, A., Reddy, S., Rotolo, M., Rice, E. : | |
| Pigs lacking the SRCR5 domain of CD163 protein demonstrate heritable resistance to the PRRS virus and no changes in animal performance from birth to maturity. Front Genome Ed 6:1322012, 2024. Pubmed reference: 38544785. DOI: 10.3389/fgeed.2024.1322012. | |
| Ren, J., Hai, T., Chen, Y., Sun, K., Han, Z., Wang, J., Li, C., Wang, Q., Wang, L., Zhu, H., Yu, D., Li, W., Zhao, S. : | |
| Improve meat production and virus resistance by simultaneously editing multiple genes in livestock using Cas12iMax. Sci China Life Sci 67:555-564, 2024. Pubmed reference: 37987939. DOI: 10.1007/s11427-023-2407-0. | |
| Rowland, R.R.R., Salgado, B., Lowe, J., Sonstegard, T.S., Carlson, D.F., Martins, K., Bostrom, J.R., Storms, S., Brandariz-Nuñez, A. : | |
| Deletion of maternal CD163 PSTII-domain-coding exon 13 protects fetuses from infection with porcine reproductive and respiratory syndrome virus (PRRSV). Vet Microbiol 298:S0378-1135(24)00277-3:110255, 2024. Pubmed reference: 39332164. DOI: 10.1016/j.vetmic.2024.110255. | |
| Salgado, B., Rivas, R.B., Pinto, D., Sonstegard, T.S., Carlson, D.F., Martins, K., Bostrom, J.R., Sinebo, Y., Rowland, R.R.R., Brandariz-Nuñez, A. : | |
| Genetically modified pigs lacking CD163 PSTII-domain-coding exon 13 are completely resistant to PRRSV infection. Antiviral Res 221:S0166-3542(24)00001-9:105793, 2024. Pubmed reference: 38184111. DOI: 10.1016/j.antiviral.2024.105793. | |
| 2023 | Pei, Y., Lin, C., Li, H., Feng, Z. : |
| Genetic background influences pig responses to porcine reproductive and respiratory syndrome virus. Front Vet Sci 10:1289570, 2023. Pubmed reference: 37929286. DOI: 10.3389/fvets.2023.1289570. | |
| Torricelli, M., Fratto, A., Ciullo, M., Sebastiani, C., Arcangeli, C., Felici, A., Giovannini, S., Sarti, F.M., Sensi, M., Biagetti, M. : | |
| Porcine reproductive and respiratory syndrome (PRRS) and CD163 resistance polymorphic markers: What is the scenario in naturally infected pig livestock in central Italy? Animals (Basel) 13:2477, 2023. Pubmed reference: 37570285. DOI: 10.3390/ani13152477. | |
| Van Goor, A., Pasternak, A., Walugembe, M., Chehab, N., Hamonic, G., Dekkers, J.C.M., Harding, J.C.S., Lunney, J.K. : | |
| Genome wide association study of thyroid hormone levels following challenge with porcine reproductive and respiratory syndrome virus. Front Genet 14:1110463, 2023. Pubmed reference: 36845393. DOI: 10.3389/fgene.2023.1110463. | |
| You, X., Li, G., Yang, Y. : | |
| Breeding for disease resistance is an effective way to solve PRRSV. Microb Pathog 182:S0882-4010(23)00284-X:106251, 2023. Pubmed reference: 37453481. DOI: 10.1016/j.micpath.2023.106251. | |
| 2022 | Stoian, A.M.M., Rowland, R.R.R., Brandariz-Nuñez, A. : |
| Mutations within scavenger receptor cysteine-rich (SRCR) protein domain 5 of porcine CD163 involved in infection with porcine reproductive and respiratory syndrome virus (PRRS). J Gen Virol 103, 2022. Pubmed reference: 35506985. DOI: 10.1099/jgv.0.001740. | |
| Tu, C.F., Chuang, C.K., Yang, T.S. : | |
| The application of new breeding technology based on gene editing in pig industry - A review. Anim Biosci 35:791-803, 2022. Pubmed reference: 34991204. DOI: 10.5713/ab.21.0390. | |
| 2021 | Kim, S., Cho, E.S., Kim, Y.S., Lim, Y., Jeong, S.A., Song, M., Lee, K.T., Kim, J.M. : |
| Novel insight into linkage disequilibrium and additive effect of GBP1 and GBP5 SNP haplotypes associated with porcine reproductive and respiratory syndrome virus susceptibility in Korean native pigs. Anim Genet 52:897-898, 2021. Pubmed reference: 34482559. DOI: 10.1111/age.13134. | |
| Singh, P., Ali, S.A. : | |
| Impact of CRISPR-Cas9-based genome engineering in farm animals. Vet Sci 8:122, 2021. Pubmed reference: 34209174. DOI: 10.3390/vetsci8070122. | |
| Tanihara, F., Hirata, M., Nguyen, N.T., Le, Q.A., Wittayarat, M., Fahrudin, M., Hirano, T., Otoi, T. : | |
| Generation of CD163-edited pig via electroporation of the CRISPR/Cas9 system into porcine in vitro-fertilized zygotes. Anim Biotechnol 32:147-154, 2021. Pubmed reference: 31558095. DOI: 10.1080/10495398.2019.1668801. | |
| Zhang, J., Khazalwa, E.M., Abkallo, H.M., Zhou, Y., Nie, X., Ruan, J., Zhao, C., Wang, J., Xu, J., Li, X., Zhao, S., Zuo, E., Steinaa, L., Xie, S. : | |
| The advancements, challenges, and future implications of the CRISPR/Cas9 system in swine research. J Genet Genomics 48:347-360, 2021. Pubmed reference: 34144928. DOI: 10.1016/j.jgg.2021.03.015. | |
| 2020 | Burkard, C., Opriessnig, T., Mileham, A.J., Stadejek, T., Ait-Ali, T., Lillico, S.G., Whitelaw, C.B.A., Archibald, A.L. : |
| Erratum for Burkard et al., "Pigs Lacking the Scavenger Receptor Cysteine-Rich Domain 5 of CD163 Are Resistant to Porcine Reproductive and Respiratory Syndrome Virus 1 Infection". J Virol 94:e00951-20, 2020. Pubmed reference: 32675378. DOI: 10.1128/JVI.00951-20. | |
| Menchaca, A., Dos Santos-Neto, P.C., Mulet, A.P., Crispo, M. : | |
| CRISPR in livestock: From editing to printing. Theriogenology 150:247-254, 2020. Pubmed reference: 32088034. DOI: 10.1016/j.theriogenology.2020.01.063. | |
| Xu, K., Zhou, Y., Mu, Y., Liu, Z., Hou, S., Xiong, Y., Fang, L., Ge, C., Wei, Y., Zhang, X., Xu, C., Che, J., Fan, Z., Xiang, G., Guo, J., Shang, H., Li, H., Xiao, S., Li, J., Li, K. : | |
| CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance. Elife 9:e57132, 2020. Pubmed reference: 32876563. DOI: 10.7554/eLife.57132. | |
| 2019 | Chen, J., Wang, H., Bai, J., Liu, W., Liu, X., Yu, D., Feng, T., Sun, Z., Zhang, L., Ma, L., Hu, Y., Zou, Y., Tan, T., Zhong, J., Hu, M., Bai, X., Pan, D., Xing, Y., Zhao, Y., Tian, K., Hu, X., Li, N. : |
| Generation of pigs resistant to highly pathogenic-porcine reproductive and respiratory syndrome virus through gene editing of CD163. Int J Biol Sci 15:481-492, 2019. Pubmed reference: 30745836. DOI: 10.7150/ijbs.25862. | |
| Guo, C., Wang, M., Zhu, Z., He, S., Liu, H., Liu, X., Shi, X., Tang, T., Yu, P., Zeng, J., Yang, L., Cao, Y., Chen, Y., Liu, X., He, Z. : | |
| Highly efficient generation of pigs harboring a partial deletion of the CD163 SRCR5 domain, which are fully resistant to porcine reproductive and respiratory syndrome virus 2 infection. Front Immunol 10:1846, 2019. Pubmed reference: 31440241. DOI: 10.3389/fimmu.2019.01846. | |
| Wang, H., Shen, L., Chen, J., Liu, X., Tan, T., Hu, Y., Bai, X., Li, Y., Tian, K., Li, N., Hu, X. : | |
| Deletion of CD163 exon 7 confers resistance to highly pathogenic porcine reproductive and respiratory viruses on pigs. Int J Biol Sci 15:1993-2005, 2019. Pubmed reference: 31523199. DOI: 10.7150/ijbs.34269. | |
| 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:e00415-18, 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:e01521-16, 2017. Pubmed reference: 27847356. DOI: 10.1128/JVI.01521-16. | |
| Whitworth, K.M., Prather, R.S. : | |
| Gene editing as applied to prevention of reproductive porcine reproductive and respiratory syndrome. Mol Reprod Dev 84:926-933, 2017. Pubmed reference: 28390179. DOI: 10.1002/mrd.22811. | |
| 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. | |
| 2015 | Zhang, Q., Yoo, D. : |
| PRRS virus receptors and their role for pathogenesis. Vet Microbiol 177:229-41, 2015. Pubmed reference: 25912022. DOI: 10.1016/j.vetmic.2015.04.002. | |
| 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. | |
| Whitworth, K.M., Lee, K., Benne, J.A., Beaton, B.P., Spate, L.D., Murphy, S.L., Samuel, M.S., Mao, J., O'Gorman, C., Walters, E.M., Murphy, C.N., Driver, J., Mileham, A., McLaren, D., Wells, K.D., Prather, R.S. : | |
| Use of the CRISPR/Cas9 system to produce genetically engineered pigs from in vitro-derived oocytes and embryos. Biol Reprod 91:78, 2014. Pubmed reference: 25100712. DOI: 10.1095/biolreprod.114.121723. | |
| 2013 | Prather, R.S., Rowland, R.R., Ewen, C., Trible, B., Kerrigan, M., Bawa, B., Teson, J.M., Mao, J., Lee, K., Samuel, M.S., Whitworth, K.M., Murphy, C.N., Egen, T., Green, J.A. : |
| An intact sialoadhesin (Sn/SIGLEC1/CD169) is not required for attachment/internalization of the porcine reproductive and respiratory syndrome virus. J Virol 87:9538-46, 2013. Pubmed reference: 23785195. DOI: 10.1128/JVI.00177-13. | |
| 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 Breedam, W., Delputte, P.L., Van Gorp, H., Misinzo, G., Vanderheijden, N., Duan, X., Nauwynck, H.J. : |
| Porcine reproductive and respiratory syndrome virus entry into the porcine macrophage. J Gen Virol 91:1659-67, 2010. Pubmed reference: 20410315. DOI: 10.1099/vir.0.020503-0. | |
| 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
- Changed by Frank Nicholas on 18 Sep 2019
- Changed by Imke Tammen2 on 24 Feb 2021
- Changed by Imke Tammen2 on 25 Jun 2021
- Changed by Imke Tammen2 on 10 Sep 2021
- Changed by Imke Tammen2 on 11 Jan 2022
- Changed by Imke Tammen2 on 18 Dec 2023
- Changed by Imke Tammen2 on 08 Jan 2024
- Changed by Imke Tammen2 on 08 Apr 2024