猪繁殖与呼吸综合征病毒生命周期的研究进展

doi:10.11843/j.issn.0366-6964.2025.03.006

摘要/Abstract

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(porcine reproductive and respiratory syndrome virus，PRRSV)引起的以猪呼吸系统疾病和母猪繁殖障碍为主要特征的传染病，给全球养猪业造成了巨大的经济损失。然而，PRRS至今仍没有安全有效的疫苗和药物进行防治。全面深入理解PRRSV生命周期可以为PRRS防控提供新的思路。因此，本文在简述PRRSV生命周期的基础上，重点对病毒侵入、复制与转录、翻译及翻译后修饰、组装等过程的研究进展进行综述，以期为PRRSV致病机制及防控研究提供参考。

关键词: 猪繁殖与呼吸综合征病毒, 入侵, 复制和转录, 翻译及翻译后修饰, 组装

Abstract:

Porcine reproductive and respiratory syndrome (PRRS) is an infectious disease caused by porcine reproductive and respiratory syndrome virus (PRRSV), which is mainly characterized by respiratory symptoms in pigs and reproductive failures in sows. PRRS has led to huge economic losses to the global swine industry. However, there is still no safe and effective vaccine or drug against PRRS. A comprehensive and in-depth understanding of the PRRSV life cycle can provide new ideas for PRRS prevention and control. Therefore, based on a brief description of the PRRSV life cycle, this paper focuses on the research progress of viral invasion, replication and transcription, translation and post-translational modification, assembly, with a view to providing a reference for the study of PRRSV pathogenic mechanism, prevention and control.

Key words: porcine reproductive and respiratory syndrome virus, invasion, replication and transcription, translation and post-translational modification, assembly

中图分类号:

S852.659.6

刘爱军, 张传亮, 黄晓兵, 周彩琴. 猪繁殖与呼吸综合征病毒生命周期的研究进展[J]. 畜牧兽医学报, 2025, 56(3): 1027-1041.

LIU Aijun, ZHANG Chuanliang, HUANG Xiaobing, ZHOU Caiqin. Research Progress on the Life Cycle of Porcine Reproductive and Respiratory Syndrome Virus[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(3): 1027-1041.

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参考文献 120

1	HOLTKAMP D J, KLIEBENSTEIN J B, ZIMMERMAN J J, et al. Economic impact of porcine reproductive and respiratory syndrome virus on U.S. pork producers[R]//Iowa State University Animal Industry Report 2012.658(1): doi: https://doi.org/10.31274/ans_air-180814-28.
2	刘小红, 陈瑶生. 2023年生猪产业与技术发展状况[J]. 中国畜牧杂志, 2024, 60 (3): 302- 307.
	LIU X H , CHEN Y S . Development of swine industry and technology in 2023[J]. Chinese Journal of Animal Science, 2024, 60 (3): 302- 307.
3	CHEN X X , QIAO S L , LI R , et al. Evasion strategies of porcine reproductive and respiratory syndrome virus[J]. Front Microbiol, 2023, 14, 1140449. doi: 10.3389/fmicb.2023.1140449
4	XIONG J Y , CUI X Y , ZHAO K , et al. A novel motif in the 3'-UTR of PRRSV-2 is critical for viral multiplication and contributes to enhanced replication ability of highly pathogenic or L1 PRRSV[J]. Viruses, 2022, 14 (2): 166. doi: 10.3390/v14020166
5	CHAUDHARI J , NGUYEN T N , VU H L X . Identification of cryptic promoter activity in cDNA sequences corresponding to PRRSV 5' untranslated region and transcription regulatory sequences[J]. Viruses, 2022, 14 (2): 400. doi: 10.3390/v14020400
6	LUNNEY J K , FANG Y , LADINIG A , et al. Porcine reproductive and respiratory syndrome virus (PRRSV): pathogenesis and interaction with the immune system[J]. Annu Rev Anim Biosci, 2016, 4, 129- 154. doi: 10.1146/annurev-animal-022114-111025
7	NAUWYNCK H J , DUAN X , FAVOREEL H W , et al. Entry of porcine reproductive and respiratory syndrome virus into porcine alveolar macrophages via receptor-mediated endocytosis[J]. J Gen Virol, 1999, 80 (2): 297- 305.
8	YANG Q , ZHANG Q , TANG J , et al. Lipid rafts both in cellular membrane and viral envelope are critical for PRRSV efficient infection[J]. Virology, 2015, 484, 170- 180. doi: 10.3760/cma.j.issn.1673-4092.2015.z1.086
9	WEI X , LI R , QIAO S L , et al. Porcine reproductive and respiratory syndrome virus utilizes viral apoptotic mimicry as an alternative pathway to infect host cells[J]. J Virol, 2020, 94 (17): e00709- 20.
10	HOU J , LI R , QIAO S L , et al. Elastase-mediated membrane fusion of highly pathogenic porcine reproductive and respiratory syndrome virus at host cell surface[J]. Vet Microbiol, 2020, 250, 108851. doi: 10.1016/j.vetmic.2020.108851
11	MA J , MA L L , YANG M T , et al. The function of the PRRSV-host interactions and their effects on viral replication and propagation in antiviral strategies[J]. Vaccines (Basel), 2021, 9 (4): 364. doi: 10.3390/vaccines9040364
12	ZHANG W , CHEN K R , ZHANG X Q , et al. An integrated analysis of membrane remodeling during porcine reproductive and respiratory syndrome virus replication and assembly[J]. PLoS One, 2018, 13 (7): e0200919. doi: 10.1371/journal.pone.0200919
13	WOOTTON S K , YOO D . Homo-oligomerization of the porcine reproductive and respiratory syndrome virus nucleocapsid protein and the role of disulfide linkages[J]. J Virol, 2003, 77 (8): 4546- 4557. doi: 10.1128/JVI.77.8.4546-4557.2003
14	BELLO-ONAGHISE G , WANG G , HAN X , et al. Antiviral strategies of Chinese herbal medicine against PRRSV infection[J]. Front Microbiol, 2020, 11, 1756. doi: 10.3389/fmicb.2020.01756
15	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.
16	WANG T , FANG L R , ZHAO F W , et al. Exosomes mediate intercellular transmission of porcine reproductive and respiratory syndrome virus[J]. J Virol, 2018, 92 (4): e01734- 17.
17	GUO R , KATZ B B , TOMICH J M , et al. Porcine reproductive and respiratory syndrome virus utilizes nanotubes for intercellular spread[J]. J Virol, 2016, 90 (10): 5163- 5175. doi: 10.1128/JVI.00036-16
18	DELPUTTE P L , VANDERHEIJDEN N , NAUWYNCK H J , et al. Involvement of the matrix protein in attachment of porcine reproductive and respiratory syndrome virus to a heparinlike receptor on porcine alveolar macrophages[J]. J Virol, 2002, 76 (9): 4312- 4320. doi: 10.1128/JVI.76.9.4312-4320.2002
19	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. doi: 10.1371/journal.ppat.1000730
20	秦梦梦. 猪CD169分子单克隆抗体制备及CD169在PRRSV感染中作用机制初探[D]. 杨凌: 西北农林科技大学, 2022.
	QIN M M. Preparation of porcine CD169 monoclonal antibody and preliminary study on the mechanism of CD169 in PRRSV infection[D]. Yangling: Northwest A&F University, 2022. (in Chinese)
21	DAS P B , DINH P X , ANSARI I H , et al. The minor envelope glycoproteins GP2a and GP4 of porcine reproductive and respiratory syndrome virus interact with the receptor CD163[J]. J Virol, 2010, 84 (4): 1731- 1740. doi: 10.1128/JVI.01774-09
22	HOU G P , XUE B Y , LI L L , et al. Direct interaction between CD163 N-terminal domain and MYH9 C-terminal domain contributes to porcine reproductive and respiratory syndrome virus internalization by permissive cells[J]. Front Microbiol, 2019, 10, 1815. doi: 10.3389/fmicb.2019.01815
23	GAO J M , XIAO S Q , XIAO Y H , et al. MYH9 is an essential factor for porcine reproductive and respiratory syndrome virus infection[J]. Sci Rep, 2016, 6 (1): 25120. doi: 10.1038/srep25120
24	SONG T , FANG L R , WANG D , et al. Quantitative interactome reveals that porcine reproductive and respiratory syndrome virus nonstructural protein 2 forms a complex with viral nucleocapsid protein and cellular vimentin[J]. J Proteomics, 2016, 142, 70- 81. doi: 10.1016/j.jprot.2016.05.009
25	LIANG Z P , LI P J , WANG C P , et al. Visualizing the transport of porcine reproductive and respiratory syndrome virus in live cells by quantum dots-based single virus tracking[J]. Virol Sin, 2020, 35 (4): 407- 416. doi: 10.1007/s12250-019-00187-0
26	WANG L , LI R , GENG R , et al. Heat shock protein member 8 (HSPA8) is involved in porcine reproductive and respiratory syndrome virus attachment and internalization[J]. Microbiol Spectr, 2022, 10 (1): e0186021. doi: 10.1128/spectrum.01860-21
27	WANG R , WANG X , WU J Q , et al. Efficient porcine reproductive and respiratory syndrome virus entry in MARC-145 cells requires EGFR-PI3K-AKT-LIMK1-COFILIN signaling pathway[J]. Virus Res, 2016, 225, 23- 32. doi: 10.1016/j.virusres.2016.09.005
28	WANG R , WANG X , NI B , et al. Syndecan-4, a PRRSV attachment factor, mediates PRRSV entry through its interaction with EGFR[J]. Biochem Biophys Res Commun, 2016, 475 (2): 230- 237. doi: 10.1016/j.bbrc.2016.05.084
29	SHANMUKHAPPA K , KIM J K , KAPIL S . Role of CD151, A tetraspanin, in porcine reproductive and respiratory syndrome virus infection[J]. Virol J, 2007, 4 (1): 62. doi: 10.1186/1743-422X-4-62
30	HUANG Y W , DRYMAN B A , LI W , et al. Porcine DC-SIGN: molecular cloning, gene structure, tissue distribution and binding characteristics[J]. Dev Comp Immunol, 2009, 33 (4): 464- 480. doi: 10.1016/j.dci.2008.09.010
31	XIE J X , CHRISTIAENS I , YANG B , et al. Preferential use of Siglec-1 or Siglec-10 by type 1 and type 2 PRRSV strains to infect PK15^S1-CD163 and PK15^S10-CD163 cells[J]. Vet Res, 2018, 49 (1): 67. doi: 10.1186/s13567-018-0569-z
32	DU Y J , PATTNAIK A K , SONG C , et al. Glycosyl-phosphatidylinositol (GPI)-anchored membrane association of the porcine reproductive and respiratory syndrome virus GP4 glycoprotein and its co-localization with CD163 in lipid rafts[J]. Virology, 2012, 424 (1): 18- 32. doi: 10.1016/j.virol.2011.12.009
33	SU C M , ROWLAND R R R , YOO D . Recent advances in PRRS virus receptors and the targeting of receptor-ligand for control[J]. Vaccines (Basel), 2021, 9 (4): 354. doi: 10.3390/vaccines9040354
34	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. doi: 10.3390/vaccines8040592
35	DENG Z F , ZHANG S K , SUN M Q , et al. Nanobodies against porcine CD163 as PRRSV broad inhibitor[J]. Int J Biol Macromol, 2023, 253, 127493. doi: 10.1016/j.ijbiomac.2023.127493
36	ZHU J Q , HE X , BERNARD D , et al. Identification of new compounds against PRRSV infection by directly targeting CD163[J]. J Virol, 2023, 97 (5): e0005423. doi: 10.1128/jvi.00054-23
37	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. doi: 10.1371/journal.ppat.1006206
38	XU K , ZHOU Y R , SHANG H T , et al. Pig macrophages with site-specific edited CD163 decrease the susceptibility to infection with porcine reproductive and respiratory syndrome virus[J]. J Integr Agric, 2023, 22 (7): 2188- 2199.
39	STOIAN A M M , ROWLAND R R R , BRANDARIZ-NUÑEZ A . Identification of CD163 regions that are required for porcine reproductive and respiratory syndrome virus (PRRSV) infection but not for binding to viral envelope glycoproteins[J]. Virology, 2022, 574, 71- 83. doi: 10.1016/j.virol.2022.07.012
40	SALGADO B , RIVAS R B , PINTO D , et al. Genetically modified pigs lacking CD163 PSTII-domain-coding exon 13 are completely resistant to PRRSV infection[J]. Antivir Res, 2024, 221, 105793. doi: 10.1016/j.antiviral.2024.105793
41	LI L L , SUN W Y , HU Q F , et al. Identification of MYH9 key domain involved in the entry of PRRSV into permissive cells[J]. Front Microbiol, 2022, 13, 865343. doi: 10.3389/fmicb.2022.865343
42	LEE W S , WHEATLEY A K , KENT S J , et al. Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies[J]. Nat Microbiol, 2020, 5 (10): 1185- 1191. doi: 10.1038/s41564-020-00789-5
43	YOON K J , WU L L , ZIMMERMAN J J , et al. Antibody-dependent enhancement (ADE) of porcine reproductive and respiratory syndrome virus (PRRSV) infection in pigs[J]. Viral Immunol, 1996, 9 (1): 51- 63. doi: 10.1089/vim.1996.9.51
44	SHI P D , SU Y X , LI Y , et al. The alternatively spliced porcine FcγRI regulated PRRSV-ADE infection and proinflammatory cytokine production[J]. Dev Comp Immunol, 2019, 90, 186- 198. doi: 10.1016/j.dci.2018.09.019
45	QIAO S L , JIANG Z Z , TIAN X H , et al. Porcine FcγRIIb mediates enhancement of porcine reproductive and respiratory syndrome virus (PRRSV) infection[J]. PLoS One, 2011, 6 (12): e28721. doi: 10.1371/journal.pone.0028721
46	GU W H , GUO L J , YU H D , et al. Involvement of CD16 in antibody-dependent enhancement of porcine reproductive and respiratory syndrome virus infection[J]. J Gen Virol, 2015, 96 (Pt 7): 1712- 1722.
47	张留君, 师瑞龙, 王焕弟, 等. Sn受体N端V-set结构域和CD163受体SRCR5结构域在PRRSV-ADE感染中的作用[J]. 中国兽医学报, 2022, 42 (12): 2458- 2463.
	ZHANG L J , SHI R L , WANG H D , et al. Roles of N-terminal V-set domain of Sn receptor and SRCR5 domain of CD163 receptor in PRRSV-ADE infection[J]. Chinese Journal of Veterinary Science, 2022, 42 (12): 2458- 2463.
48	张峥, 孙雨晨, 范阔海, 等. PAMs免疫粘附受体CR 1-like对PRRSV感染的影响[J]. 山西农业大学学报: 自然科学版, 2023, 43 (2): 100- 110.
	ZHANG Z , SUN Y C , FAN K H , et al. Effects of porcine alveolar macrophages immune adhesive receptor CR1-like on PRRSV infection[J]. Journal of Shanxi Agricultural University: Natural Science Edition, 2023, 43 (2): 100- 110.
49	HOU J , LI R , QIAO S L , et al. Glycoprotein 5 is cleaved by cathepsin E during porcine reproductive and respiratory syndrome virus membrane fusion[J]. J Virol, 2020, 94 (10): e00097- 20.
50	SONG J W , GAO P , KONG C , et al. The nsp2 hypervariable region of porcine reproductive and respiratory syndrome virus strain JXwn06 is associated with viral cellular tropism to primary porcine alveolar macrophages[J]. J Virol, 2019, 93 (24): e01436- 19.
51	ZHANG A K , DUAN H , ZHAO H J , et al. Interferon-induced transmembrane protein 3 is a virus-associated protein which suppresses porcine reproductive and respiratory syndrome virus replication by blocking viral membrane fusion[J]. J Virol, 2020, 94 (24): e01350- 20.
52	MISINZO G M , DELPUTTE P L , NAUWYNCK H J . Involvement of proteases in porcine reproductive and respiratory syndrome virus uncoating upon internalization in primary macrophages[J]. Vet Res, 2008, 39 (6): 55. doi: 10.1051/vetres:2008031
53	YU P , WEI R P , DONG W J , et al. CD163^ΔSRCR5 MARC-145 cells resist PRRSV-2 infection via inhibiting virus uncoating, which requires the interaction of CD163 with calpain 1[J]. Front Microbiol, 2020, 10, 3115. doi: 10.3389/fmicb.2019.03115
54	WIßING M H , BRVGGEMANN Y , STEINMANN E , et al. Virus-host cell interplay during hepatitis E virus infection[J]. Trends Microbiol, 2021, 29 (4): 309- 319. doi: 10.1016/j.tim.2020.07.002
55	WANG X , CHEN Y W , QI C Y , et al. Mechanism, structural and functional insights into nidovirus-induced double-membrane vesicles[J]. Front Immunol, 2024, 15, 1340332. doi: 10.3389/fimmu.2024.1340332
56	NAN H , LAN J X , TIAN M M , et al. The network of interactions among porcine reproductive and respiratory syndrome virus non-structural proteins[J]. Front Microbiol, 2018, 9, 970. doi: 10.3389/fmicb.2018.00970
57	ZHAO S S , QIAN Q S , CHEN X X , et al. Porcine reproductive and respiratory syndrome virus triggers Golgi apparatus fragmentation-mediated autophagy to facilitate viral self-replication[J]. J Virol, 2024, 98 (2): e0184223. doi: 10.1128/jvi.01842-23
58	V'KOVSKI P , GERBER M , KELLY J , et al. Determination of host proteins composing the microenvironment of coronavirus replicase complexes by proximity-labeling[J]. eLife, 2019, 8, e42037. doi: 10.7554/eLife.42037
59	FANG P X , XIE C B , PAN T , et al. Unfolding of an RNA G-quadruplex motif in the negative strand genome of porcine reproductive and respiratory syndrome virus by host and viral helicases to promote viral replication[J]. Nucleic Acids Res, 2023, 51 (19): 10752- 10767. doi: 10.1093/nar/gkad759
60	ZHAO S C , GE X N , WANG X L , et al. The DEAD-box RNA helicase 5 positively regulates the replication of porcine reproductive and respiratory syndrome virus by interacting with viral Nsp9 in vitro[J]. Virus Res, 2015, 195, 217- 224. doi: 10.1016/j.virusres.2014.10.021
61	LI J , WANG D , FANG P X , et al. DEAD-box RNA helicase 21 (DDX21) positively regulates the replication of porcine reproductive and respiratory syndrome virus via multiple mechanisms[J]. Viruses, 2022, 14 (3): 467. doi: 10.3390/v14030467
62	LIU L , TIAN J , NAN H , et al. Porcine reproductive and respiratory syndrome virus nucleocapsid protein interacts with Nsp9 and cellular DHX9 to regulate viral RNA synthesis[J]. J Virol, 2016, 90 (11): 5384- 5398. doi: 10.1128/JVI.03216-15
63	BEURA L K , DINH P X , OSORIO F A , et al. Cellular poly(C) binding proteins 1 and 2 interact with porcine reproductive and respiratory syndrome virus nonstructural protein 1β and support viral replication[J]. J Virol, 2011, 85 (24): 12939- 12949. doi: 10.1128/JVI.05177-11
64	ZHANG A G , SUN Y T , JING H Y , et al. Interaction of HnRNP F with the guanine-rich segments in viral antigenomic RNA enhances porcine reproductive and respiratory syndrome virus-2 replication[J]. Virol J, 2022, 19 (1): 82. doi: 10.1186/s12985-022-01811-4
65	SONG Y N , GUO Y Y , LI X Y , et al. RBM39 alters phosphorylation of c-Jun and binds to viral RNA to promote PRRSV proliferation[J]. Front Immunol, 2021, 12, 664417. doi: 10.3389/fimmu.2021.664417
66	WANG X Y , BAI J , ZHANG L L , et al. Poly (A)-binding protein interacts with the nucleocapsid protein of porcine reproductive and respiratory syndrome virus and participates in viral replication[J]. Antivir Res, 2012, 96 (3): 315- 323. doi: 10.1016/j.antiviral.2012.09.004
67	GAO P , CHAI Y , SONG J W , et al. Reprogramming the unfolded protein response for replication by porcine reproductive and respiratory syndrome virus[J]. PLoS Pathog, 2019, 15 (11): e1008169. doi: 10.1371/journal.ppat.1008169
68	ZHENG Z F , FU X L , LING X , et al. Host cells actively resist porcine reproductive and respiratory syndrome virus infection via the IRF8-MicroRNA-10a-SRP14 regulatory pathway[J]. J Virol, 2022, 96 (7): e0000322. doi: 10.1128/jvi.00003-22
69	GAO J T , XIAO S Q , LIU X H , et al. Inhibition of HSP70 reduces porcine reproductive and respiratory syndrome virus replication in vitro[J]. BMC Microbiol, 2014, 14, 64. doi: 10.1186/1471-2180-14-64
70	SONG C H , LIU H Z , CAO Z , et al. HSP27 interacts with nonstructural proteins of porcine reproductive and respiratory syndrome virus and promotes viral replication[J]. Pathogens, 2023, 12 (1): 91. doi: 10.3390/pathogens12010091
71	DONG S , LIU L , WU W N , et al. Determination of the interactome of non-structural protein12 from highly pathogenic porcine reproductive and respiratory syndrome virus with host cellular proteins using high throughput proteomics and identification of HSP70 as a cellular factor for virus replication[J]. J Proteomics, 2016, 146, 58- 69. doi: 10.1016/j.jprot.2016.06.019
72	CHANG X B , YANG Y Q , GAO J C , et al. Annexin A2 binds to vimentin and contributes to porcine reproductive and respiratory syndrome virus multiplication[J]. Vet Res, 2018, 49 (1): 75. doi: 10.1186/s13567-018-0571-5
73	WANG Q M , YI H Y , GUO Y C , et al. PCNA promotes PRRSV replication by increasing the synthesis of viral genome[J]. Vet Microbiol, 2023, 281, 109741. doi: 10.1016/j.vetmic.2023.109741
74	WANG M D , YANG L , MENG J J , et al. Functionally active cyclin-dependent kinase 9 is essential for porcine reproductive and respiratory syndrome virus subgenomic RNA synthesis[J]. Mol Immunol, 2021, 135, 351- 364. doi: 10.1016/j.molimm.2021.05.004
75	ZHANG L , PAN Y , XU Y F , et al. Paraoxonase-1 facilitates PRRSV replication by interacting with viral nonstructural protein-9 and inhibiting type I interferon pathway[J]. Viruses, 2022, 14 (6): 1203. doi: 10.3390/v14061203
76	ZHU Z B , XU Y Q , CHEN L L , et al. Bergamottin inhibits PRRSV replication by blocking viral non-structural proteins expression and viral RNA synthesis[J]. Viruses, 2023, 15 (6): 1367. doi: 10.3390/v15061367
77	SONG J W , LIU Y Y , GAO P , et al. Mapping the nonstructural protein interaction network of porcine reproductive and respiratory syndrome virus[J]. J Virol, 2018, 92 (24): e01112- 18.
78	SHA H Y , ZHANG H , CHEN Y , et al. Research progress on the NSP9 protein of porcine reproductive and respiratory syndrome virus[J]. Front Vet Sci, 2022, 9, 872205.
79	LI G , ZHENG Y J , LUO Q , et al. Research progress on the NSP10 protein of porcine reproductive and respiratory syndrome virus[J]. Microorganisms, 2024, 12 (3): 553. doi: 10.3390/microorganisms12030553
80	ZHENG Y J , ZHANG H , LUO Q , et al. Research progress on NSP11 of porcine reproductive and respiratory syndrome virus[J]. Vet Sci, 2023, 10 (7): 451.
81	WANG T Y , FANG Q Q , CONG F , et al. The Nsp12-coding region of type 2 PRRSV is required for viral subgenomic mRNA synthesis[J]. Emerg Microbes Infect, 2019, 8 (1): 1501- 1510. doi: 10.1080/22221751.2019.1679010
82	DENG H , XIN N , ZENG F C , et al. A novel amino acid site of N protein could affect the PRRSV-2 replication by regulating the viral RNA transcription[J]. BMC Vet Res, 2022, 18 (1): 171. doi: 10.1186/s12917-022-03274-9
83	ISELIN L , PALMALUX N , KAMEL W , et al. Uncovering viral RNA-host cell interactions on a proteome-wide scale[J]. Trends Biochem Sci, 2022, 47 (1): 23- 38. doi: 10.1016/j.tibs.2021.08.002
84	ROZMAN B , FISHER T , STERN-GINOSSAR N . Translation-a tug of war during viral infection[J]. Mol cell, 2023, 83 (3): 481- 495. doi: 10.1016/j.molcel.2022.10.012
85	李洋. PRRSV调控细胞翻译和自噬的机制研究[D]. 武汉: 华中农业大学, 2020.
	LI Y. The mechanism of PRRSV regulating cell translation and autophagy[D]. Wuhan: Huazhong Agricultural University, 2020. (in Chinese)
86	WEI R P , ZHANG X X , WANG X Y , et al. PDCD4 restricts PRRSV replication in an eIF4A-dependent manner and is antagonized by the viral nonstructural protein 9[J]. J Virol, 2024, 98 (5): e0006024. doi: 10.1128/jvi.00060-24
87	李华玮, 王旭英, 乔宏兴, 等. 慢病毒载体介导的稳定表达eIF5A细胞系的建立及其对猪繁殖与呼吸综合征病毒增殖的影响[J]. 畜牧兽医学报, 2023, 54 (3): 1169- 1176.
	LI H W , WANG X Y , QIAO H X , et al. Establishment of a lentiviral vector-mediated stable expression of eIF5A cell line and its effect on porcine reproductive and respiratory syndrome virus propagation[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54 (3): 1169- 1176.
88	李华玮, 王旭英, 井汇源, 等. eIF5A基因敲除MARC-145多克隆细胞系的建立及其对PRRSV增殖的影响[J]. 中国农业大学学报, 2023, 28 (7): 122- 129.
	LI H W , WANG X Y , JING H Y , et al. Establishment of eIF5A gene knockout polyclonal MARC-145 cell line and its effect on PRRSV infection[J]. Journal of China Agricultural University, 2023, 28 (7): 122- 129.
89	YOO D , WOOTTON S K , LI G , et al. Colocalization and interaction of the porcine arterivirus nucleocapsid protein with the small nucleolar RNA-associated protein fibrillarin[J]. J Virol, 2003, 77 (22): 12173- 12183. doi: 10.1128/JVI.77.22.12173-12183.2003
90	KE H Z , HAN M Y , KIM J , et al. Porcine reproductive and respiratory syndrome virus nonstructural protein 1 beta interacts with nucleoporin 62 to promote viral replication and immune evasion[J]. J Virol, 2019, 93 (14): e00469- 19.
91	殷杰, 赵永祥, 薛江东, 等. 核糖体蛋白L12(RPL12)在猪繁殖与呼吸综合征病毒复制中的作用[J]. 江苏农业学报, 2021, 37 (3) doi: 10.3969/j.issn.1000-4440.2021.03.017
	YIN J , ZHAO Y X , XUE J D , et al. Role of ribosomal protein L12 (RPL12) in porcine reproductive and respiratory syndrome virus replication[J]. Jiangsu Journal of Agricultural Sciences, 2021, 37 (3): 686- 693. doi: 10.3969/j.issn.1000-4440.2021.03.017
92	KUMAR R , MEHTA D , MISHRA N , et al. Role of host-mediated post-translational modifications (PTMs) in RNA virus pathogenesis[J]. Int J Mol Sci, 2020, 22 (1): 323.
93	ZHAO P D , JING H Y , DONG W , et al. TRIM26-mediated degradation of nucleocapsid protein limits porcine reproductive and respiratory syndrome virus-2 infection[J]. Virus Res, 2022, 311, 198690. doi: 10.1016/j.virusres.2022.198690
94	BAI Y Z , LI L W , SHAN T L , et al. Proteasomal degradation of nonstructural protein 12 by RNF114 suppresses porcine reproductive and respiratory syndrome virus replication[J]. Vet Microbiol, 2020, 246, 108746. doi: 10.1016/j.vetmic.2020.108746
95	CHEN J , ZHAO S J , CUI Z Y , et al. MicroRNA-376b-3p promotes porcine reproductive and respiratory syndrome virus replication by targeting viral restriction factor TRIM22[J]. J Virol, 2022, 96 (2): e01597- 21.
96	CUI Z Y , ZHOU L K , ZHAO S J , et al. The host E3-ubiquitin ligase TRIM28 impedes viral protein GP4 ubiquitination and promotes prrsv replication[J]. Int J Mol Sci, 2023, 24 (13): 10965. doi: 10.3390/ijms241310965
97	GUO R , YAN X Y , LI Y H , et al. A swine arterivirus deubiquitinase stabilizes two major envelope proteins and promotes production of viral progeny[J]. PLoS Pathog, 2021, 17 (3): e1009403. doi: 10.1371/journal.ppat.1009403
98	LI R Q , CHEN C , HE J , et al. E3 ligase ASB8 promotes porcine reproductive and respiratory syndrome virus proliferation by stabilizing the viral Nsp1α protein and degrading host IKKβ kinase[J]. Virology, 2019, 532, 55- 68. doi: 10.1016/j.virol.2019.04.004
99	LI X Y , SUN R Q , GUO Y Y , et al. N-acetyltransferase 9 inhibits porcine reproductive and respiratory syndrome virus proliferation by N-terminal acetylation of the structural protein GP5[J]. Microbiol Spectr, 2022, 11 (1): e02442- 22.
100	易和友, 于之清, 陈耀, 等. N蛋白磷酸化位点突变影响猪繁殖与呼吸综合征病毒的复制及亚基因组的转录[J]. 畜牧兽医学报, 2019, 50 (12): 2470- 2478. doi: 10.11843/j.issn.0366-6964.2019.12.011
	YI H Y , YU Z Q , CHEN Y , et al. Mutation of N protein phosphorylation site affects replication and subgenomic transcription of porcine reproductive and respiratory syndrome virus[J]. Acta Veterinaria et Zootechnica Sinica, 2019, 50 (12): 2470- 2478. doi: 10.11843/j.issn.0366-6964.2019.12.011
101	SHANG P C , YUAN F F , MISRA S , et al. Hyper-phosphorylation of nsp2-related proteins of porcine reproductive and respiratory syndrome virus[J]. Virology, 2020, 543, 63- 75. doi: 10.1016/j.virol.2020.01.018
102	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. doi: 10.1016/j.virol.2010.12.002
103	RUPASINGHE R , LEE K , LIU X , et al. Molecular evolution of porcine reproductive and respiratory syndrome virus field strains from two swine production systems in the Midwestern United States from 2001 to 2020[J]. Microbiol Spectr, 2022, 10 (3): e0263421.
104	ZHANG M Z , HAN X L , OSTERRIEDER K , et al. Palmitoylation of the envelope membrane proteins GP5 and M of porcine reproductive and respiratory syndrome virus is essential for virus growth[J]. PLoS Pathog, 2021, 17 (4): e1009554. doi: 10.1371/journal.ppat.1009554
105	ZHENG Z F , LING X , LI Y , et al. Host cells reprogram lipid droplet synthesis through YY1 to resist PRRSV infection[J]. mBio, 2024, 15 (8): e01549- 24.
106	LAVAL T , OUIMET M . A role for lipophagy in atherosclerosis[J]. Nat Rev Cardiol, 2023, 20 (7): 431- 432. doi: 10.1038/s41569-023-00885-z
107	LI G L , HAN Y Q , SU B Q , et al. Porcine reproductive and respiratory syndrome virus 2 hijacks CMA-mediated lipolysis through upregulation of small GTPase RAB18[J]. PLoS Pathog, 2024, 20 (4): e1012123. doi: 10.1371/journal.ppat.1012123
108	WANG J , LIU J Y , SHAO K Y , et al. Porcine reproductive and respiratory syndrome virus activates lipophagy to facilitate viral replication through downregulation of NDRG1 expression[J]. J Virol, 2019, 93 (17): e00526- 19.
109	YU P W , FU P F , ZENG L , et al. EGCG restricts PRRSV proliferation by disturbing lipid metabolism[J]. Microbiol Spectr, 2022, 10 (2): e02276- 21.
110	DAI J , FENG Y Y , LIAO Y , et al. ESCRT machinery and virus infection[J]. Antiviral Res, 2024, 221, 105786. doi: 10.1016/j.antiviral.2023.105786
111	ZHANG L X , LI R , GENG R , et al. Tumor susceptibility gene 101 (TSG101) contributes to virion formation of porcine reproductive and respiratory syndrome virus via interaction with the nucleocapsid (N) protein along with the early secretory pathway[J]. J Virol, 2022, 96 (6): e00005- 22.
112	WARREN C J , YU S Q , PETERS D K , et al. Primate hemorrhagic fever-causing arteriviruses are poised for spillover to humans[J]. Cell, 2022, 185 (21): 3980- 3991. e18. doi: 10.1016/j.cell.2022.09.022
113	DU T F , NAN Y C , XIAO S Q , et al. Antiviral strategies against PRRSV infection[J]. Trends Microbiol, 2017, 25 (12): 968- 979. doi: 10.1016/j.tim.2017.06.001
114	TANG H P , GAO Y , HAN J Y . Application progress of the single domain antibody in medicine[J]. Int J Mol Sci, 2023, 24 (4): 4176. doi: 10.3390/ijms24044176
115	DE VLIEGER D , BALLEGEER M , ROSSEY I , et al. Single-domain antibodies and their formatting to combat viral infections[J]. Antibodies (Basel), 2018, 8 (1): 1. doi: 10.3390/antib8010001
116	BUTHELEZI L A , PILLAY S , NTULI N N , et al. Antisense therapy for infectious diseases[J]. Cells, 2023, 12 (16): 2119. doi: 10.3390/cells12162119
117	HAN X , FAN S M , PATEL D , et al. Enhanced inhibition of porcine reproductive and respiratory syndrome virus replication by combination of morpholino oligomers[J]. Antiviral Res, 2009, 82 (1): 59- 66. doi: 10.1016/j.antiviral.2009.01.009
118	OPRIESSNIG T , PATEL D , WANG R , et al. Inhibition of porcine reproductive and respiratory syndrome virus infection in piglets by a peptide-conjugated morpholino oligomer[J]. Antiviral Res, 2011, 91 (1): 36- 42. doi: 10.1016/j.antiviral.2011.04.012
119	REN J H , DUAN H , DONG H X , et al. TAT nanobody exerts antiviral effect against PRRSV in vitro by targeting viral nucleocapsid protein[J]. Int J Mol Sci, 2023, 24 (3): 1905. doi: 10.3390/ijms24031905
120	DUAN H , CHEN X , ZHANG Z W , et al. A nanobody inhibiting porcine reproductive and respiratory syndrome virus replication via blocking self-interaction of viral nucleocapsid protein[J]. J Virol, 2024, 98 (1): e0131923. doi: 10.1128/jvi.01319-23

受体/因子 Receptors/factor	PRRSV结合因子 PRRSV binding partner	主要功能 Main function	参考文献 Reference
HS	M	参与介导病毒黏附	[18]
Sn	GP5/M N	参与介导病毒黏附和内化参与介导病毒内化	[19] [20]
CD163	GP2/GP4	介导病毒黏附、内化和脱壳	[21]
MYH9	GP5	介导病毒内化	[22, 23]
vimentin	Nsp2和N蛋白	与病毒黏附和内化有关	[24, 25]
HSPA8	GP4	促进病毒黏附，协同CD163参与病毒内化	[26]
TIM1/4	凋亡类似物磷脂酰丝氨酸	介导巨胞饮途径内化	[9]
EGFR	尚不清楚	调节肌动蛋白的碎裂和重组，促进内化	[27]
Syndecan-4	尚不清楚	参与介导黏附和内化	[28]
CD151	3′UTR	与感染相关，但具体机制尚不清楚	[29]
CD209	尚不清楚	与感染相关，但具体机制尚不清楚	[30]
Siglec-10	GP5	参与介导病毒黏附和内化	[31]

宿主因子 Host factor	PRRSV结合因子 PRRSV binding partner	生物学功能 Biological function	参考文献 Reference
DDX18	负链gRNA的G4结构	解开G4结构，促进gRNA复制	[59]
DDX5	Nsp9	促进gRNA复制	[60]
DDX21	Nsp1β	稳定PRRSV Nsp1α、Nsp1β和N蛋白的表达	[61]
DHX9	N	解开PRRSV RNA二级结构，促进gRNA复制和长链sgRNA转录	[62]
HnRNP E1和E2	5′UTR/Nsp1β	促进PRRSV gRNA复制和转录	[63]
HnRNP F	负链gRNA G4结构	促进PRRSV gRNA复制	[64]
RBM39	vRNA	可能通过稳定PRRSV RNA，促进病毒复制	[65]
PABP	N	促进PRRSV gRNA复制	[66]
ATF4	Nsp2/3和vRNA	促进PRRSV gRNA复制	[67]
SRP14	Nsp2	促进PRRSV gRNA复制	[68]
HSP27	Nsp1α、Nsp1β、Nsp5、Nsp9、 Nsp11和nsp12	促进PRRSV gRNA复制	[70]
HSP70	Nsp12	促进PRRSV gRNA复制	[71]
ANXA2	Nsp9	促进PRRSV gRNA复制	[72]
PCNA	Nsp9、Nsp12和N	促进PRRSV gRNA复制	[73]
CDK9	尚不清楚	促进PRRSV sgRNA合成	[74]
PON1	Nsp9	促进PRRSV gRNA复制	[75]

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