畜牧兽医学报 ›› 2023, Vol. 54 ›› Issue (2): 434-442.doi: 10.11843/j.issn.0366-6964.2023.02.002
刘铃1,2, 王丹丹1, 崔凯2, 马月辉1, 蒋琳1*
收稿日期:
2022-06-17
出版日期:
2023-02-23
发布日期:
2023-02-21
通讯作者:
蒋琳,主要从事动物种质资源研究,E-mail:jianglin@caas.cn
作者简介:
刘铃(1998-),女,四川安岳人,硕士生,主要从事动物遗传育种与繁殖研究,E-mail:LiuuLingg602@163.com
基金资助:
LIU Ling1,2, WANG Dandan1, CUI Kai2, MA Yuehui1, JIANG Lin1*
Received:
2022-06-17
Online:
2023-02-23
Published:
2023-02-21
摘要: 猪繁殖与呼吸综合征(porcine reproductive and respiratory syndrome,PRRS)是由猪繁殖与呼吸综合征病毒(PRRS virus,PRRSV)引起的一种高度接触性传染病,严重危害我国乃至世界养猪业。然而由于PRRSV抗原的多变性,目前包括疫苗接种、药物治疗等在内的防治措施效果不佳。因此,随着现代分子生物学技术的不断发展,基于基因编辑技术对猪PRRS的抗病育种逐渐发展起来。本文简述了PRRS的临床症状,重点回顾了国内外PRRS抗病育种研究进展,通过分析PRRS的致病机制,重点阐述了PRRSV受体及针对不同受体进行编辑的体内及体外抗病毒效果,以期为未来深入研究PRRSV致病机制、开发PRRS抗病品种提供理论依据。
中图分类号:
刘铃, 王丹丹, 崔凯, 马月辉, 蒋琳. 猪繁殖与呼吸综合征抗病育种研究进展[J]. 畜牧兽医学报, 2023, 54(2): 434-442.
LIU Ling, WANG Dandan, CUI Kai, MA Yuehui, JIANG Lin. Advances of Disease-Resistant Breeding on Porcine Reproductive and Respiratory Syndrome[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(2): 434-442.
[1] | 刘小红, 陈瑶生.2021年生猪产业发展状况、未来发展趋势与建议[J].中国畜牧杂志, 2022, 58(3):204-209.LIU X H, CHEN Y S.Development tatus, trend in future and suggestion of pig industry in 2021[J].Chinese Journal of Animal Science, 2022, 58(3):204-209.(in Chinese) |
[2] | 齐丹丹, 刘佳欣.基于支持向量机的中国猪肉产量预测研究[J].中国商论, 2021(1):18-20.QI D D, LIU J X.Research on China pork production forecast based on support vector machine[J].China Journal of Commerce, 2021(1):18-20.(in Chinese) |
[3] | WU C Y, GU G Q, ZHAI T S, et al.Broad neutralization activity against both PRRSV-1 and PRRSV-2 and enhancement of cell mediated immunity against PRRSV by a novel IgM monoclonal antibody[J].Antiviral Res, 2020, 175:104716. |
[4] | LIU J K, XU Y, LIN Z F, et al.Epidemiology investigation of PRRSV discharged by faecal and genetic variation of ORF5[J].Transbound Emerg Dis, 2021, 68(4):2334-2344. |
[5] | LIANG C, LIU H L, ZHOU J M, et al.Development of a monoclonal antibody against PRRSV glycoprotein 3 using an immuodominant peptide as immunogen[J].Int J Biol Macromol, 2021, 187:683-689. |
[6] | 吴 瑕, 劳梦琴, 谭祥梅, 等.2017-2020年我国部分地区PRRSV流行毒株变异情况分析[J].中国动物传染病学报, 2021, 29(5):64-74.WU X, LAO M Q, TAN X M, et al.Analysis on variation of PRRSV epidemic strains in some areas of China[J].Chinese Journal of Animal Infectious Diseases, 2021, 29(5):64-74.(in Chinese) |
[7] | CHEN J Y, WANG H T, BAI J H, et al.Generation of pigs resistant to highly pathogenic-porcine reproductive and respiratory syndrome virus through gene editing of CD163[J].Int J Biol Sci, 2019, 15(2):481-492. |
[8] | BURKARD C, OPRIESSNIG T, MILEHAM A J, 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].J Virol, 2018, 92(16):e00415-18. |
[9] | 王增辉, 王洪亮.中小规模猪场蓝耳病防控策略[J].中国畜禽种业, 2022, 18(4):111-112.WANG Z H, WANG H L.Prevention and control strategy of PRRS in small and medium-sized pig farms[J].The Chinese Livestock and Poultry Breeding, 2022, 18(4):111-112.(in Chinese) |
[10] | LAGER K M, HALBUR P G.Gross and microscopic lesions in porcine fetuses infected with porcine reproductive and respiratory syndrome virus[J].J Vet Diagn Invest, 1996, 8(3):275-282. |
[11] | 曹金明.猪繁殖与呼吸障碍综合征诊断及防治[J].畜牧兽医科学(电子版), 2020(17):65-66.CAO J M.Diagnosis and prevention of swine reproductive and respiratory syndrome[J].Graziery Veterinary Sciences (Electronic Version), 2020(17):65-66.(in Chinese) |
[12] | LIU J, YAO L, HUANG S G, et al.AMG487 inhibits PRRSV replication and ameliorates lung injury in pig lung xenografts by down-regulating the expression of ANXA2[J].Antiviral Res, 2022, 202:105314. |
[13] | YOU X B, QU Y L, ZHANG Y, et al.Mir-331-3p Inhibits PRRSV-2 Replication and Lung Injury by Targeting PRRSV-2 ORF1b and Porcine TNF-α[J].Front Immunol, 2020, 11:547144. |
[14] | GRAY D K, DVORAK C M T, ROBINSON S R, et al.Characterization of age-related susceptibility of macrophages to porcine reproductive and respiratory syndrome virus[J].Virus Res, 2019, 263:139-144. |
[15] | XU H L, LIU Z H, ZHENG S Y, et al.CD163 Antibodies inhibit PRRSV infection via receptor blocking and transcription suppression[J].Vaccines (Basel), 2020, 8(4):592. |
[16] | GUO C H, ZHU Z B, GUO Y, et al.Heparanase upregulation contributes to porcine reproductive and respiratory syndrome virus release[J].J Virol, 2017, 91(15):e00625-17. |
[17] | OH D, XIE J X, VANDERHEIJDEN N, et al.Isolation and characterization of a new population of nasal surface macrophages and their susceptibility to PRRSV-1 subtype 1 (LV) and subtype 3 (Lena)[J].Vet Res, 2020, 51(1):21. |
[18] | XU K, ZHOU Y R, MU Y L, et al.CD163 and pAPN double-knockout pigs are resistant to PRRSV and TGEV and exhibit decreased susceptibility to PDCoV while maintaining normal production performance[J].Elife, 2020, 9:e57132. |
[19] | DELPUTTE P L, COSTERS S, NAUWYNCK H J.Analysis of porcine reproductive and respiratory syndrome virus attachment and internalization:distinctive roles for heparan sulphate and sialoadhesin[J].J Gen Virol, 2005, 86(5):1441-1445. |
[20] | LI R, QIAO S L, ZHANG G P.Reappraising host cellular factors involved in attachment and entry to develop antiviral strategies against porcine reproductive and respiratory syndrome virus[J].Front Microbiol, 2022, 13:975610. |
[21] | CAO S L, LIU J Q, DING G F, et al.The tail domain of PRRSV NSP2 plays a key role in aggrephagy byinteracting with 14-3-3ε[J].Vet Res, 2020, 51(1):104. |
[22] | DAS P B, VU H L X, DINH P X, et al.Glycosylation of minor envelope glycoproteins of porcine reproductive and respiratory syndrome virus in infectious virus recovery, receptor interaction, and immune response[J].Virology, 2011, 410(2):385-394. |
[23] | PAN X C, ZHANG N Z, WEI X H, et al.Illumination of PRRSV cytotoxic T lymphocyte epitopes by the three-dimensional structure and peptidome of swine lymphocyte antigen class I (SLA-I)[J].Front Immunol, 2019, 10:2995. |
[24] | SUN W F, WU W X, JIANG N, et al.Highly pathogenic PRRSV-infected alveolar macrophages impair the function of pulmonary microvascular endothelial cells[J].Viruses, 2022, 14(3):452. |
[25] | RUKARCHEEP D, LOTHONG M, WATTANAPHANSAK S, et al.Porcine reproductive and respiratory syndrome virus induces tight junction barrier dysfunction and cell death in porcine glandular endometrial epithelial cells[J].Theriogenology, 2022, 185:34-42. |
[26] | MENG X J, HALBUR P G, SHAPIRO M S, et al.Genetic and experimental evidence for cross-species infection by swine hepatitis E virus[J].J Virol, 1998, 72(12):9714-9721. |
[27] | PETRY D B, HOLL J W, WEBER J S, et al.Biological responses to porcine respiratory and reproductive syndrome virus in pigs of two genetic populations[J].J Anim Sci, 2005, 83(7):1494-1502. |
[28] | PETRY D B, LUNNEY J, BOYD P, et al.Differential immunity in pigs with high and low responses to porcine reproductive and respiratory syndrome virus infection[J].J Anim Sci, 2007, 85(9):2075-2092. |
[29] | AIT-ALI T, WILSON A D, WESTCOTT D G, et al.Innate immune responses to replication of porcine reproductive and respiratory syndrome virus in isolated Swine alveolar macrophages[J].Viral Immunol, 2007, 20(1):105-118. |
[30] | LUNNEY J K, STEIBEL J P, REECY J M, et al.Probing genetic control of swine responses to PRRSV infection:current progress of the PRRS host genetics consortium[J].BMC Proc, 2011, 5 Suppl 4(Suppl 4):S30. |
[31] | DONG Q, DUNKELBERGER J, LIM K S, et al.Associations of natural variation in the CD163 and other candidate genes on host response of nursery pigs to porcine reproductive and respiratory syndrome virus infection[J].J Anim Sci, 2021, 99(10):skab274. |
[32] | WHITWORTH K M, ROWLAND R R R, EWEN C L, et al.Gene-edited pigs are protected from porcine reproductive and respiratory syndrome virus[J].Nat Biotechnol, 2016, 34(1):20-22. |
[33] | BODDICKER N J, BJORKQUIST A, ROWLAND R R, et al.Genome-wide association and genomic prediction for host response to porcine reproductive and respiratory syndrome virus infection[J].Genet Sel Evol, 2014, 46(1):18. |
[34] | DUCHET-SUCHAUX M F, BERTIN A M, MENANTEAU P S.Susceptibility of Chinese Meishan and European large white pigs to enterotoxigenic Escherichia coli strains bearing colonization factor K88, 987P, K99, or F41[J].Am J Vet Res, 1991, 52(1):40-44. |
[35] | MALLARD B A, DEKKERS J C, IRELAND M J, et al.Alteration in immune responsiveness during the peripartum period and its ramification on dairy cow and calf health[J].J Dairy Sci, 1998, 81(2):585-595. |
[36] | WILKIE B, MALLARD B.Selection for high immune response:an alternative approach to animal health maintenance?[J]. Vet Immunol Immunopathol, 1999, 72(1-2):231-235. |
[37] | LI G Y, JIANG H Y, CHANG M, et al.HDAC6 α-tubulin deacetylase:a potential therapeutic target in neurodegenerative diseases[J].J Neurol Sci, 2011, 304(1-2):1-8. |
[38] | LU T Y, SONG Z Y, LI Q Y, et al.Overexpression of histone deacetylase 6 enhances resistance to porcine reproductive and respiratory syndrome virus in pigs[J].PLoS One, 2017, 12(1):e0169317. |
[39] | WHITWORTH K M, LEE K, BENNE J A, et al.Use of the CRISPR/Cas9 system to produce genetically engineered pigs from in vitro-derived oocytes and embryos[J].Biol Reprod, 2014, 91(3):78. |
[40] | YU P, WEI R P, DONG W J, et al. MARC-145 cells resist PRRSV-2 infection via inhibiting virus uncoating, which requires the interaction of CD163 with Calpain 1[J].Front Microbiol, 2019, 10:3115. |
[41] | 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].J Gen Virol, 2022, 103(5):001740. |
[42] | ZHANG Q Z, YOO D.PRRS virus receptors and their role for pathogenesis[J].Vet Microbiol, 2015, 177(3-4):229-241. |
[43] | CALVERT J G, SLADE D E, SHIELDS S L, et al.CD163 expression confers susceptibility to porcine reproductive and respiratory syndrome viruses[J].J Virol, 2007, 81(14):7371-7379. |
[44] | VAN GORP H, DELPUTTE P L, NAUWYNCK H J.Scavenger receptor CD163, a Jack-of-all-trades and potential target for cell-directed therapy[J].Mol Immunol, 2010, 47(7-8):1650-1660. |
[45] | PATTON J B, ROWLAND R R, YOO D, et al.Modulation of CD163 receptor expression and replication of porcine reproductive and respiratory syndrome virus in porcine macrophages[J].Virus Res, 2009, 140(1-2):161-171. |
[46] | HUANG C, BERNARD D, ZHU J Q, et al.Small molecules block the interaction between porcine reproductive and respiratory syndrome virus and CD163 receptor and the infection of pig cells[J].Virol J, 2020, 17(1):116. |
[47] | FABRIEK B O, VAN BRUGGEN R, DENG D M, et al.The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria[J].Blood, 2009, 113(4):887-892. |
[48] | WANG X P, WEI R F, LI Q Y, et al.PK-15 cells transfected with porcine CD163 by PiggyBac transposon system are susceptible to porcine reproductive and respiratory syndrome virus[J].J Virol Methods, 2013, 193(2):383-390. |
[49] | GUO L J, NIU J W, YU H D, et al.Modulation of CD163 expression by metalloprotease ADAM17 regulates porcine reproductive and respiratory syndrome virus entry[J].J Virol, 2014, 88(18):10448-10458. |
[50] | WELLS K D, BARDOT R, WHITWORTH K M, et al.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].J Virol, 2017, 91(2):e01521-16. |
[51] | BURKARD C, LILLICO S G, REID E, et al.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[J].PLoS Pathog, 2017, 13(2):e1006206. |
[52] | YANG H Q, ZHANG J, ZHANG X W, et al.CD163 knockout pigs are fully resistant to highly pathogenic porcine reproductive and respiratory syndrome virus[J].Antiviral Res, 2018, 151:63-70. |
[53] | GUO C H, WANG M, ZHU Z B, et al.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[J].Front Immunol, 2019, 10:1846. |
[54] | WANG P, WANG Z, LIU J.Role of HDACs in normal and malignant hematopoiesis[J].Mol Cancer, 2020, 19(1):5. |
[55] | HUBBERT C, GUARDIOLA A, SHAO R, et al.HDAC6 is a microtubule-associated deacetylase[J].Nature, 2002, 417(6887):455-458. |
[56] | GAO Y S, HUBBERT C C, LU J R, et al.Histone deacetylase 6 regulates growth factor-induced actin remodeling and endocytosis[J].Mol Cell Biol, 2007, 27(24):8637-8647. |
[57] | VALENZUELA-FERNÁNDEZ A, CABRERO J R, SERRADOR J M, et al.HDAC6:a key regulator of cytoskeleton, cell migration and cell-cell interactions[J].Trends Cell Biol, 2008, 18(6):291-297. |
[58] | ZHU J Z, COYNE C B, SARKAR S N.PKC alpha regulates Sendai virus-mediated interferon induction through HDAC6 and β-catenin[J].EMBO J, 2011, 30(23):4838-4849. |
[59] | BRUSH M H, GUARDIOLA A, CONNOR J H, et al.Deactylase inhibitors disrupt cellular complexes containing protein phosphatases and deacetylases[J].J Biol Chem, 2004, 279(9):7685-7691. |
[60] | 袁林林, 王 峰, 李晟磊, 等.组蛋白去乙酰化酶6表达下调对喉鳞癌Hep-2细胞增殖细胞周期和迁移能力的影响[J].中华肿瘤杂志, 2012, 34(6):430-435.YUAN L L, WANG F, LI S L, et al.Effects of downregulation of HDAC6 expression on cell cycle, proliferation and migration of laryngeal squamous cell carcinoma[J].Chinese Journal of Oncology, 2012, 34(6):430-435.(in Chinese) |
[61] | VANDERHEIJDEN N, DELPUTTE P L, FAVOREEL H W, et al.Involvement of sialoadhesin in entry of porcine reproductive and respiratory syndrome virus into porcine alveolar macrophages[J].J Virol, 2003, 77(15):8207-8215. |
[62] | DELPUTTE P L, MEERTS P, COSTERS S, et al.Effect of virus-specific antibodies on attachment, internalization and infection of porcine reproductive and respiratory syndrome virus in primary macrophages[J].Vet Immunol Immunopathol, 2004, 102(3):179-188. |
[63] | DELPUTTE P L, NAUWYNCK H J.Porcine arterivirus infection of alveolar macrophages is mediated by sialic acid on the virus[J].J Virol, 2004, 78(15):8094-8101. |
[64] | VAN BREEDAM W, VAN GORP H, ZHANG J Q, et al.The M/GP5 glycoprotein complex of porcine reproductive and respiratory syndrome virus binds the sialoadhesin receptor in a sialic acid-dependent manner[J].PLoS Pathog, 2010, 6(1):e1000730. |
[65] | VAN BREEDAM W, DELPUTTE P L, VAN GORP H, et al.Porcine reproductive and respiratory syndrome virus entry into the porcine macrophage[J].J Gen Virol, 2010, 91(Pt 7):1659-1667. |
[66] | PRATHER R S, ROWLAND R R R, EWEN C, et al.An intact sialoadhesin (Sn/SIGLEC1/CD169) is not required for attachment/internalization of the porcine reproductive and respiratory syndrome virus[J].J Virol, 2013, 87(17):9538-9546. |
[67] | JANIK E, NIEMCEWICZ M, CEREMUGA M, et al.Various aspects of a gene editing system-CRISPR-Cas9[J].Int J Mol Sci, 2020, 21(24):9604. |
[68] | GARNEAU J E, DUPUIS M ō, VILLION M, et al.The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA[J].Nature, 2010, 468(7320):67-71. |
[69] | GASIUNAS G, BARRANGOU R, HORVATH P, et al.Cas9-crRNA ribonucleoprotein complex mediates specific DNA cleavage for adaptive immunity in bacteria[J].Proc Natl Acad Sci U S A, 2012, 109(39):E2579-E2586. |
[70] | CONG L, RAN F A, COX D, et al.Multiplex genome engineering using CRISPR/Cas systems[J].Science, 2013, 339(6121):819-823. |
[71] | JASIN M, MOYNAHAN M E, RICHARDSON C.Targeted transgenesis[J].Proc Natl Acad Sci U S A, 1996, 93(17):8804-8808. |
[72] | 余传照, 莫健新, 赵 鑫, 等.基于CRISPR/Cas系统的DNA碱基编辑技术及其在生物医学和农业中的应用[J].生物工程学报, 2021, 37(9):3071-3087.YU C Z, MO J X, ZHAO X, et al.CRISPR/Cas-mediated DNA base editing technology and its application in biomedicine and agriculture[J].Chinese Journal of Biotechnology, 2021, 37(9):3071-3087.(in Chinese) |
[73] | RATNER L D, LA MOTTA G E, BRISKI O, et al.Practical approaches for knock-out gene editing in pigs[J].Front Genet, 2021, 11:617850. |
[74] | REINER G.Genetic resistance-an alternative for controlling PRRS?[J].Porcine Health Manag, 2016, 2:27. |
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