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组蛋白去乙酰化酶抑制剂对小反刍兽疫病毒复制的影响
引用本文:潘春容,邓瑞雪,胡林杰,朱学亮,孙跃峰,王桂荣,蒙学莲.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.
作者姓名:潘春容  邓瑞雪  胡林杰  朱学亮  孙跃峰  王桂荣  蒙学莲
作者单位:1. 甘肃农业大学动物医学院, 兰州 730070;2. 中国农业科学院兰州兽医研究所, 家畜疫病病原生物学国家重点实验室, 兰州 730046
基金项目:中国农业科学院科技创新工程专项经费(CAAS-ASTIP-LVRI-2021)
摘    要:旨在探究组蛋白去乙酰化酶抑制剂对小反刍兽疫病毒(peste des petits ruminants virus,PPRV)复制的影响,以确定组蛋白去乙酰化酶(histone deacetylases,HDACs)在PPRV复制过程中的作用。采用RT-qPCR法检测PPRV感染后Vero细胞HDACs(HDAC1~11) mRNA表达水平的变化;用针对不同类型HDACs的抑制剂处理感染PPRV的Vero细胞48 h,Western blot筛选影响PRPV N蛋白表达的抑制剂;应用筛选出的抑制剂处理感染PPRV的Vero细胞,通过RT-qPCR、Western blot和TCID50法进一步分析抑制剂对病毒RNA、蛋白和病毒滴度的影响。结果显示,PPRV感染后,Vero细胞HDAC2 mRNA水平显著升高(P<0.05);SAHA、TMP269、MGCD0103处理后,PPRV N蛋白的表达量明显降低,且呈剂量负相关;SAHA、TMP269、MGCD0103也显著降低PPRV N RNA表达水平(P<0.05,P<0.05,P<0.01)和病毒滴度(P<0.05,P<0.05,P<0.01)。这表明Ⅱa类HDACs抑制剂和Ⅰ类HDACs抑制剂能抑制PPRV的复制,Ⅰ类HDACs (HDAC1~3)和Ⅱa类HDACs (HDAC4~5、HDAC7、HDAC9)可能参与调控PPRV的感染。

关 键 词:组蛋白去乙酰化酶抑制剂  组蛋白去乙酰化酶  小反刍兽疫病毒  复制  
收稿时间:2021-12-06

Effect of Histone Deacetylase Inhibitors on Peste Des Petits Ruminants Virus Replication
PAN Chunrong,DENG Ruixue,HU Linjie,ZHU Xueliang,SUN Yuefeng,WANG Guirong,MENG Xuelian.Effect of Histone Deacetylase Inhibitors on Peste Des Petits Ruminants Virus Replication[J].Acta Veterinaria et Zootechnica Sinica,2022,53(7):2307-2316.
Authors:PAN Chunrong  DENG Ruixue  HU Linjie  ZHU Xueliang  SUN Yuefeng  WANG Guirong  MENG Xuelian
Institution:1. College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China;2. State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China
Abstract:The present study aimed to explore the effect of histone deacetylase(HDAC) inhibitors on peste des petits ruminants virus (PPRV) replication, and to determine the role of HDACs involved in the PPRV replication.The mRNA expression of HDACs (HDAC1-11) was examined by RT-qPCR assay in PPRV-infected Vero cells. To screen the inhibitors that affect PPRV replication, the expression level of N protein was evaluated in infected Vero cells by Western blot following treatment with the various inhibitors for different types of HDACs for 48 h. The selected inhibitors were used to treat PPRV-infected Vero cells, and the effects of inhibitors on PPRV N RNA, N protein and virus titer were further analyzed by RT-qPCR, Western blot and TCID50, respectively. The results showed that PPRV infection in Vero cells resulted in a significant increase of the mRNA expression level of HDAC2 (P<0.05). After treatment with SAHA, TMP269 and MGCD0103, the expression level of PPRV N protein was significantly reduced and negatively correlated with the doses of these inhibitors. SAHA, TMP269 and MGCD0103 also significantly reduced the expression level of PPRV N RNA (P<0.05, P<0.05, P<0.01) and virus titer (P<0.05, P<0.05, P<0.01), respectively. These results indicated that class IIa HDACs inhibitors and class I HDACs inhibitors significantly inhibited PPRV replication in Vero cells, suggesting that class I HDACs (HDAC1-3) and class IIa HDACs (HDAC4-5, HDAC7, HDAC9) may be involved in the regulation of PPRV infection.
Keywords:histone deacetylase inhibitor  histone deacetylase  peste des petits ruminants virus  replication  
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