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Cross-inhibition to heterologous foot-and-mouth disease virus infection induced by RNA interference targeting the conserved regions of viral genome

文献类型: 外文期刊

作者: Liu, MQ 1 ; Chen, WZ 2 ; Ni, Z 2 ; Yan, WY 2 ; Fei, L 3 ; Jiao, Y; Zhang, J; Du, QY; Wei, X; Chen, JL; Liu, YM; Zhe 1 ;

作者机构: 1.Fudan Univ, Sch Life Sci, Genet Inst, State Key Lab Genet Engn, Shanghai 200433, Peoples R China

2.Fudan Univ, Sch Life Sci, Genet Inst, State Key Lab Genet Engn, Shanghai 200433, Peoples R China; Zhejiang Acad Agr Sci, Inst Biotechnol, Hangzhou 310021, Peoples R China; Jinyu Grp Co Ltd, Biopharm, Inner Mongolia 010020, Peoples R China

3.Fudan Univ, Sch Life Sci, Genet Inst, State Key Lab Genet Engn, Shanghai 200433, Peoples R China; Zhejiang Acad Agr Sci, Inst Biotechnol, Hangzhou 310021, Peoples R China; Jinyu Grp Co Ltd, Biopharm, Inner

关键词: FMDV;RNA interference (RNAi);cross-inhibition;conserved region;viral genome;EMERGENCY VACCINATION;MAMMALIAN-CELLS;CONTACT TRANSMISSION;SECONDARY STRUCTURE;ANTIVIRAL IMMUNITY;REPLICATION;POLYMERASE;REDUCTION;SIRNA;IDENTIFICATION

期刊名称:VIROLOGY ( 影响因子:3.616; 五年影响因子:3.967 )

ISSN:

年卷期:

页码:

收录情况: SCI

摘要: RNA interference (RNAi) is the process by which double-stranded RNA (dsRNA) directs sequence-specific degradation of messenger RNA in animal and plant cells. In mammalian cells, RNAi can be triggered by 21-23 nucleotide duplexes of small interfering RNA (siRNA). Strategies to inhibit RNA virus Multiplication based on the use of siRNAs have to consider the high genetic polymorphism exhibited by this group of virus. F ere we described a significant cross-inhibition of foot-and-mouth disease (FMD) virus (FMDV) replication in BHK-21 cells by siRNAs targeted to various conserved regions (5'NCR, VP4, VPg, POL, and YNCR) of the viral genome. The results showed that siRNAs generated in vitro by human recombinant dicer enzyme gave ail inhibition of 10- to 1000-fold in virus yield of both homologous (HKN/2002) and heterologom (CHA/99) isolates of FMDV serotype O at 48 h post-infection (hpi). The inhibition extended to at least 6 days postinfection. For serotype Asial, the virus yield in YNBS/58-infected cells examined at 12, 24, and 48 hpi decreased by ∼ 10-fold in cells pretreated with FKN/2002-specific siRNAs, but there was no significant decrease at 60 hpi. The inhibition was specific to FMDV replication, as no reduction was observed in virus yield of pseudorabies virus, an unrelated virus. Moreover, we also demonstrated an enhanced viral suppression could be achieved in BHK-21 cells with siRNA transfection after an infection had been established. These results suggested that siRNAs directed to several conserved regions of the FMDV genome Could inhibit FMDV replication in a cross-resistance manner, providing a strategy candicate to treat high genetic variability of FMDV. © 2005 Elsevier Inc. All rights reserved.

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