组蛋白去乙酰化酶抑制剂MGCD0103对小反刍兽疫病毒体外复制的影响

doi:10.11843/j.issn.0366-6964.2024.10.025

Abstract

Abstract:

In this study, the effect of MGCD0103 (Mocetinostat), a selective HDACi, on the replication of peste des petits ruminants virus (PPRV) in goat endometrial epithelial cells (EEC cells) was investigated, aiming to clarify the role and activity of MGCD0103 in PPRV multiplication. The transcription levels of HDACs and PPRV N gene in different treated cells were determined by RT-qPCR, and the action stage of MGCD0103 in the viral proliferation cycle of PPRV was determined by the time of addition assay. The effect of MGCD0103 on the expression level of PPRV N protein and viral titer were further analyzed by Western blot and TCID₅₀, respectively. The results showed that the mRNA expression levels of HDAC1 (P < 0.001) and HDAC2 (P < 0.002) were increased significantly in PPRV-infected EEC cells. Although MGCD0103 has an excellent inhibitory effect on PPRV multiplication, its inhibitory effect in the virus entry is limited. MGCD0103 significantly reduced the transcription and expression levels of PPRV N gene, as well as the viral titer (P < 0.002). The half-maximal effective concentration (EC₅₀) and selectivity index (SI) of MGCD0103 against PPRV were 0.43 μmol·L^-1 and 4.35, respectively. These results indicated that MGCD0103 significantly inhibited PPRV replication, which is of great significance for the development of anti-PPRV drugs and provides a new idea for constructing sensitive cell lines for PPRV proliferation.

Key words: histone deacetylase inhibitor, MGCD0103, inhibit, peste des petits ruminants virus, replication

CLC Number:

Ruixue DENG, Chunrong PAN, Xueliang ZHU, Linjie HU, Yuefeng SUN, Qiaoying ZENG, Xuelian MENG. Suppressive Effect of Histone Deacetylase Inhibitor MGCD0103 on Peste Des Petits Rumants Virus Replication in vitro[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(10): 4542-4552.

Figures/Tables 9

Table 1

Fig. 1

Fig. 2

Fig. 3

Fig. 4

Fig. 5

Fig. 6

Fig. 7

Fig. 8

References 39

1	RAHEEL R , ASHRAF M , EJAZ S , et al. Assessment of the cytotoxic and anti-viral potential of aqueous extracts from different parts of Acacia nilotica (Linn) Delile against Peste des petits ruminants virus[J]. Environ Toxicol Pharmacol, 2013, 35 (1): 72- 81. doi: 10.1016/j.etap.2012.11.005
2	YADAV P , CHOUDHURY S , BARUA S , et al. Polyalthia longifolia leaves methanolic extract targets entry and budding of viruses-an in vitro experimental study against paramyxoviruses[J]. J Ethnopharmacol, 2020, 248, 112279. doi: 10.1016/j.jep.2019.112279
3	SAADH M . Epigallocatechin gallate (EGCG) combined with zinc sulfate inhibits Peste des petits ruminants virus entry and replication[J]. Saudi J Biol Sci, 2021, 28 (11): 6674- 6678. doi: 10.1016/j.sjbs.2021.07.035
4	KHANDELWAL N , KAUR G , CHAUBEY K K , et al. Silver nanoparticles impair Peste des petits ruminants virus replication[J]. Virus Res, 2014, 190, 1- 7. doi: 10.1016/j.virusres.2014.06.011
5	SUJATHA K , SHANTHI G , SELVAM N P , et al. Synthesis and antiviral activity of 4, 4'-(arylmethylene)bis(1H-pyrazol-5-ols) against peste des petits ruminant virus (PPRV)[J]. Bioorg Med Chem Lett, 2009, 19 (15): 4501- 4503. doi: 10.1016/j.bmcl.2009.02.113
6	CHANG Q Y , GUO F C , LI X R , et al. The IMPDH inhibitors, ribavirin and mycophenolic acid, inhibit peste des petits ruminants virus infection[J]. Vet Res Commun, 2018, 42 (4): 309- 313. doi: 10.1007/s11259-018-9733-1
7	JIN L , LI Y C , PU F Y , et al. Inhibiting pyrimidine biosynthesis impairs Peste des Petits Ruminants Virus replication through depletion of nucleoside pools and activation of cellular immunity[J]. Vet Microbiol, 2021, 260, 109186. doi: 10.1016/j.vetmic.2021.109186
8	GUISE A J , BUDAYEVA H G , DINER B A , et al. Histone deacetylases in herpesvirus replication and virus-stimulated host defense[J]. Viruses, 2013, 5 (7): 1607- 1632. doi: 10.3390/v5071607
9	PHIEL C J , ZHANG F , HUANG E Y , et al. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen[J]. J Biol Chem, 2001, 276 (39): 36734- 36741. doi: 10.1074/jbc.M101287200
10	UNAL G , TURAN B , BALCIOGLU Y H . Immunopharmacological management of COVID-19:Potential therapeutic role of valproic acid[J]. Med Hypotheses, 2020, 143, 109891. doi: 10.1016/j.mehy.2020.109891
11	JONES K , NOURSE J , CORBETT G , et al. Sodium valproate in combination with ganciclovir induces lysis of EBV-infected lymphoma cells without impairing EBV-specific T-cell immunity[J]. Int J Lab Hematol, 2010, 32 (1 Pt 1): e169- e174.
12	GHOSH S K , PERRINE S P , WILLIAMS R M , et al. Histone deacetylase inhibitors are potent inducers of gene expression in latent EBV and sensitize lymphoma cells to nucleoside antiviral agents[J]. Blood, 2012, 119 (4): 1008- 1017. doi: 10.1182/blood-2011-06-362434
13	SHAPIRA L , RALPH M , TOMER E , et al. Histone deacetylase inhibitors reduce the number of herpes simplex virus-1 genomes initiating expression in individual cells[J]. Front Microbiol, 2016, 7, 1970.
14	LU C Y , CHANG Y C , HUA C H , et al. Tubacin, an HDAC6 selective inhibitor, reduces the replication of the japanese encephalitis virus via the decrease of viral RNA synthesis[J]. Int J Mol Sci, 2017, 18 (5): 954. doi: 10.3390/ijms18050954
15	FENG Q Q , SU Z L , SONG S Y , et al. Histone deacetylase inhibitors suppress RSV infection and alleviate virus-induced airway inflammation[J]. Int J Mol Med, 2016, 38 (3): 812- 822. doi: 10.3892/ijmm.2016.2691
16	WIGHTMAN F , ELLENBERG P , CHURCHILL M , et al. HDAC inhibitors in HIV[J]. Immunol Cell Biol, 2012, 90 (1): 47- 54. doi: 10.1038/icb.2011.95
17	LI Y X , SETO E . HDACs and HDAC inhibitors in cancer development and therapy[J]. Cold Spring Harb Perspect Med, 2016, 6 (10): a026831. doi: 10.1101/cshperspect.a026831
18	潘春容, 邓瑞雪, 胡林杰, 等. 组蛋白去乙酰化酶抑制剂对小反刍兽疫病毒复制的影响[J]. 畜牧兽医学报, 2022, 53 (7): 2307- 2316. doi: 10.11843/j.issn.0366-6964.2022.07.027
	PAN C R , DENG R X , HU L J , et al. Effect of histone deacetylase inhibitors on Peste Des Petits ruminants virus replication[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53 (7): 2307- 2316. doi: 10.11843/j.issn.0366-6964.2022.07.027
19	BUGLIO D , MAMIDIPUDI V , KHASKHELY N M , et al. The class-Ⅰ HDAC inhibitor MGCD0103 induces apoptosis in Hodgkin lymphoma cell lines and synergizes with proteasome inhibitors by an HDAC6-independent mechanism[J]. Br J Haematol, 2010, 151 (4): 387- 396. doi: 10.1111/j.1365-2141.2010.08342.x
20	EL-KHOURY V , MOUSSAY E , JANJI B , et al. The histone deacetylase inhibitor MGCD0103 induces apoptosis in B-cell chronic lymphocytic leukemia cells through a mitochondria-mediated caspase activation cascade[J]. Mol Cancer Ther, 2010, 9 (5): 1349- 1360. doi: 10.1158/1535-7163.MCT-09-1000
21	WEI Y , KADIA T , TONG W G , et al. The combination of a histone deacetylase inhibitor with the Bcl-2 homology domain-3 mimetic GX15-070 has synergistic antileukemia activity by activating both apoptosis and autophagy[J]. Clin Cancer Res, 2010, 16 (15): 3923- 3932. doi: 10.1158/1078-0432.CCR-10-0032
22	CHIA K M , BEAMISH H , JAFFERI K , et al. The histone deacetylase inhibitor MGCD0103 has both deacetylase and microtubule inhibitory activity[J]. Mol Pharmacol, 2010, 78 (3): 436- 443. doi: 10.1124/mol.110.065169
23	CHAKRABARTY B , DAS D , BULUSU G , et al. Network-based analysis of fatal comorbidities of COVID-19 and potential therapeutics[J]. IEEE/ACM Trans Comput Biol Bioinform, 2021, 18 (4): 1271- 1280. doi: 10.1109/TCBB.2021.3075299
24	TANG J Y , TANG A X , DU H Y , et al. Peste des petits ruminants virus exhibits cell-dependent interferon active response[J]. Front Cell Infect Microbiol, 2022, 12, 874936. doi: 10.3389/fcimb.2022.874936
25	王丹阳, 张康, 王旭荣, 等. 诃子、矮紫堇、甘青乌头提取物对牛病毒性腹泻病毒的体外抑制作用[J]. 畜牧兽医学报, 2018, 49 (9): 2036- 2043. doi: 10.11843/j.issn.0366-6964.2018.09.025
	WANG D Y , ZHANG K , WANG X R , et al. Inhibitory effects of extracts from Terminalia chebula, Corydalis hendersonii, Aconitum tanguticum on bovine viral diarrhea virus in vitro[J]. Acta Veterinaria et Zootechnica Sinica, 2018, 49 (9): 2036- 2043. doi: 10.11843/j.issn.0366-6964.2018.09.025
26	LIU Z S , XUAN B Q , TANG S B , et al. Histone deacetylase inhibitor SAHA induces expression of fatty acid-binding protein 4 and inhibits replication of human cytomegalovirus[J]. Virol Sin, 2021, 36 (6): 1352- 1362. doi: 10.1007/s12250-021-00382-y
27	ZHOU Y , WANG Q , YANG Q , et al. Histone deacetylase 3 inhibitor suppresses hepatitis c virus replication by regulating apo-A1 and LEAP-1 expression[J]. Virol Sin, 2018, 33 (5): 418- 428. doi: 10.1007/s12250-018-0057-7
28	SATO A , SAITO Y , SUGIYAMA K , et al. Suppressive effect of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) on hepatitis C virus replication[J]. J Cell Biochem, 2013, 114 (9): 1987- 1996. doi: 10.1002/jcb.24541
29	ZHANG H J , WANG X W , QU M , et al. Foot-and-mouth disease virus structural protein VP3 interacts with HDAC8 and promotes its autophagic degradation to facilitate viral replication[J]. Autophagy, 2023, 19 (11): 2869- 2883. doi: 10.1080/15548627.2023.2233847
30	KOBAYASHI Y , GÉLINAS C , DOUGHERTY J P . Histone deacetylase inhibitors containing a benzamide functional group and a pyridyl cap are preferentially effective human immunodeficiency virus-1 latency-reversing agents in primary resting CD4⁺ T cells[J]. J Gen Virol, 2017, 98 (4): 799- 809. doi: 10.1099/jgv.0.000716
31	ARCHIN N M , LIBERTY A L , KASHUBA A D , et al. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy[J]. Nature, 2012, 487 (7408): 482- 485. doi: 10.1038/nature11286
32	XU J D , MAO J Y , HAN X , et al. Porcine epidemic diarrhea virus inhibits HDAC1 expression to facilitate its replication via binding of its nucleocapsid protein to host transcription factor Sp1[J]. J Virol, 2021, 95 (18): e0085321. doi: 10.1128/JVI.00853-21
33	ICARDI L , LIEVENS S , MORI R , et al. Opposed regulation of type Ⅰ IFN-induced STAT3 and ISGF3 transcriptional activities by histone deacetylases (HDACS) 1 and 2[J]. FASEB J, 2012, 26 (1): 240- 249. doi: 10.1096/fj.11-191122
34	BEGUM S , NOORUZZAMAN M , HASNAT A , et al. Isolation of peste des petits ruminants virus using primary goat kidney cell culture from kidneys obtained at slaughter[J]. Vet Med Sci, 2021, 7 (3): 915- 922. doi: 10.1002/vms3.413
35	CLARKE B D , ISLAM M R , YUSUF M A , et al. Molecular detection, isolation and characterization of Peste-des-petits ruminants virus from goat milk from outbreaks in Bangladesh and its implication for eradication strategy[J]. Transbound Emerg Dis, 2018, 65 (6): 1597- 1604. doi: 10.1111/tbed.12911
36	KUMAR N , CHAUBEY K K , CHAUDHARY K , et al. Isolation, identification and characterization of a Peste des Petits Ruminants virus from an outbreak in Nanakpur, India[J]. J Virol Methods, 2013, 189 (2): 388- 392. doi: 10.1016/j.jviromet.2013.03.002
37	EL-SABBAGH O I , EL-SADEK M E , EL-KALYOUBI S , et al. Synthesis, DNA binding and antiviral activity of new uracil, xanthine, and pteridine derivatives[J]. Arch Pharm (Weinheim), 2007, 340 (1): 26- 31. doi: 10.1002/ardp.200600149
38	ZHANG W F , DENG H L , LIU Y F , et al. Antiviral effectivity of favipiravir against peste des petits ruminants virus is mediated by the JAK/STAT and PI3K/AKT pathways[J]. Front Vet Sci, 2021, 8, 722840. doi: 10.3389/fvets.2021.722840
39	KHANDELWAL N , CHANDER Y , RAWAT K D , et al. Emetine inhibits replication of RNA and DNA viruses without generating drug-resistant virus variants[J]. Antiviral Res, 2017, 144, 196- 204. doi: 10.1016/j.antiviral.2017.06.006

引物 Primer	NCBI参考序列 NCBI reference sequence	序列(5′→3′) Sequence (5′→3′)
N-F	KY628761.1	TCGCGAGAGTTCATCCTCTTG
N-R		AAAGCGAACACGCTCAGGAA
cACTB-F	NM_001314342.1	CCTGGACTTCGAGCAGGAGA
cACTB-R		AGGCTGGAAGAGAGCCTCAG
cHDAC1-F	XM_004005023.4	TGGAAATCTATCGCCCTCACAAAGC
cHDAC1-R		ACCGACGTTGAATCTCTGCATCTG
cHDAC2-F	XM_004011189.4	CAGTCAAGGAGGCGGCAAGAAG
cHDAC2-R		AGCAAGTTATGGGTCATGCGGATC
cHDAC3-F	XM_004008901.5	CATGCACCTAGCGTCCAGATTCAC
cHDAC3-R		TCTCCTCCGCATCAGCCTCATC
cHDAC4-F	XM_042244213.1	GCTTCTGAACCCAACCTGAAATTGC
cHDAC4-R		CGCCGAGTCTGTGACATCCAAG
cHDAC5-F	XM_042256050.1	AATGTGAATGTGGCATGGACAGGAG
cHDAC5-R		CAGGTGAGAACTCGTGGGCAATG
cHDAC6-F	XM_027962812.2	TTAGCCAAACAGCCGAGCAAGAC
cHDAC6-R		AACACCAAACCAGTGCCAGACAG
cHDAC7-F	XM_042246807.1	AAACCCAACCTCAATGCCATCCG
cHDAC7-R		CGTCACTGCCTCCACTTCTTCTG
cHDAC8-F	XM_004022188.5	GCTTCCACACCGATGCCTATCTG
cHDAC8-R		CTTCAGTGGCTGGGCAGTCATAAC
cHDAC9-F	XM_042248296.1	AAAGCCCAATAGCAGCCACCAAG
cHDAC9-R		GGAACTCCACCAGCCACAAGAAG
cHDAC10-F	XM_042247939.1	TACTTCTCCTGGCACCGCTACG
cHDAC10-R		CAGGGCAGGTTGACAGTGAAGC
cHDAC11-F	XM_042236456.1	CATCATCGCCGACTCCATCCTTAAC
cHDAC11-R		GCGTGTCTGAGTTCTGTGCTGAG

[1]	Xufei FENG, Yuxiang QI, Hanzhe YU, Zhengzhou ZHANG, Rujia WANG, Chuang MENG, Kui DONG. Effect of Rab32 on the Replication of Avian Metapneumovirus Type C [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(9): 4041-4050.
[2]	XU Hong, SHANG Hongqi, ZHANG Xue, QIAN Jiali, WANG Chuanhong, SONG Xu, BAO Meiying, LIU Shiyu, ZHANG Gege, GUO Rongli, ZHAO Yongxiang, FAN Baochao, LI Bin. Inhibition Effect of C8orf4 Gene Encoding Protein on in vitro Replication of Porcine Epidemic Diarrhea Virus [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(5): 2100-2108.
[3]	ZHANG Shengying, LIU Zhongli, GUO Aijiang, WANG Shuai. The Effect of Seven Protease Inhibitors on Activity of DNA Damage Inducible 1 Protein in Echinococcus multilocularis [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(5): 2273-2280.
[4]	MA Yajuan, SU Kai, LIN Yidan, WANG Yawen, ZHANG Yanan, YUAN Hongxing, YUAN Chen, SONG Qinye. The Inhibitory Effect of Salinomycin on Porcine Epidemic Diarrhea Virus in vitro [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(4): 1661-1671.
[5]	LI Zhaolong, KONG Xiangrui, LIN Fengqiang, WANG Xiuping, ZHAO Ran, PENG Xiaoli, CHEN Changsong. Preliminary Study of the Mechanism of Inhibition of Salmonella Typhimurium by Ec-12 Supernatant [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(2): 739-750.
[6]	SONG Wenyan, ZHANG Hanwen, WU Aodi, ZHANG Liyan, LIU Zhao, YE Tongtong, CHEN Chuangfu, SHENG Jinliang. Screening of Nanobodies against Porcine Reproductive and Respiratory Syndrome Virus GP5 Protein and Exploration of Their Inhibitory Effect on Virus Replication [J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(1): 258-270.
[7]	WANG Yu, GAO Yueyi, GAO Jinyuan, LIU Weijie, XU Huilin, XUE Qinghong. Establishment of Reverse Genetics System of Peste des petits Ruminants Virus Clone9 Strain [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(7): 2956-2963.
[8]	CHENG Xiangning, ZHANG Yun, HE Jiawei, CHEN Zhengkun, JIN Meilan, DING Honglei, WANG Qinghua. Isolation, Identification and Antifungal Susceptibility Analysis of Candida albicans Isolated from Pigeons [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(7): 3002-3011.
[9]	FANG Yuan, HOU Qiaodi, XIANG Chaohui, ZHAO Hongyi, QI Xuefeng. Regulatory Effects of IFITM3 on Proliferation of Peste des Petits Ruminants Virus (PPRV) in Goat Endometrial Epithelial Cells [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(5): 2200-2207.
[10]	WANG Lan, HE Mingyu, ZHANG Min, DING Juntao. MicroRNAs Regulate Antiviral Immunity and Viral Replication [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(2): 463-472.
[11]	CHEN Junzhen, QUAN Ran, FU Qiang, GE Lijuan, YUAN Yuanyuan, ZHANG Chengyuan, LI Jianlin, SHI Huijun. Study on the Effect of Heat Shock Protein HSP90B1 on the Replication of Bovine Viral Diarrhea Virus [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(2): 683-693.
[12]	JIA Yiquan, YU Mengting, LIU Weirong, FANG Shouguo, ZHANG Songbai. Baicalin Inhibits Infectious Bronchitis Virus Replication via Promoting the Expression of Type Ⅰ Interferon [J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(11): 4839-4850.
[13]	CAO Qingguo, GUO Qin, PENG Kai, CAI Jiahui, REN Chengwan, LI Yunting. The Inhibition and Mechanism of the Combination of Berberine Hydrochloride and Levofloxacin on MRSA [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(9): 3208-3220.
[14]	YANG Fuchun, LIU Rui, LI Xiaohan, GAO Li, LIU Changjun, QI Xiaole, CUI Hongyu, WANG Xiaomei, GAO Yulong, LI Kai. Construction of UL41 Gene Deletion Strain of Duck Enteritis Virus and Analysis of Its Replication Ability in vitro [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(8): 2689-2696.
[15]	YUAN Xingguo, SHEN Chaochao, ZHAO Dengshuai, YANG Bo, CUI Huimei, HAO Yu, YANG Jinke, CHEN Xuehui, ZHANG Ting, ZHANG Keshan, LIU Xia, ZHENG Haixue, LIU Xiangtao. β-estradiol and Progesterone Promote Replication of African Swine Fever Virus in vitro [J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(7): 2252-2259.

Suppressive Effect of Histone Deacetylase Inhibitor MGCD0103 on Peste Des Petits Rumants Virus Replication in vitro

RichHTML

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 9

References 39

Related Articles 15

Recommended Articles

Metrics

Comments