反义寡核苷酸的体外和体内抗甲型流感病毒活性

In vitro and in vivo anti-influenza A virus activity of antisense oligonucleotides.

作者信息

Abe T, Mizuta T, Suzuki S, Hatta T, Takai K, Yokota T, Takaku H

机构信息

Department of Industrial Chemistry, Chiba Institute of Technology, Japan.

出版信息

Nucleosides Nucleotides. 1999 Jun-Jul;18(6-7):1685-8. doi: 10.1080/07328319908044823.

DOI:10.1080/07328319908044823

PMID:10474246

Abstract

We have demonstrated that antisense phosphorothioate oligonucleotides (S-ODNs) inhibit influenza virus A replication in MDCK cells. The liposomally encapsulated and the free antisense phosphorothioate oligonucleotides with four target sites (PB1, PB2, PA, and NP) were tested for their abilities to inhibit virus-induced cytopathogenic effects by a MTT assay using MDCK cells. The liposomally encapsulated S-ODN complementary to the sites of the PB2-AUG initiation codon showed highly inhibitory effects. Therefore, the antiviral effects of S-ODN-PB2-AUG and PA-AUG were examined in a mouse model of influenza virus A infection. PB2-AUG oligomer treated i.v. significantly prolonged the mean survival time in day (MDS) and increased the survival rates with does dependent manner.

摘要

我们已经证明，反义硫代磷酸酯寡核苷酸（S-ODNs）可抑制甲型流感病毒在MDCK细胞中的复制。使用MDCK细胞，通过MTT试验检测了具有四个靶位点（PB1、PB2、PA和NP）的脂质体包裹型和游离反义硫代磷酸酯寡核苷酸抑制病毒诱导的细胞病变效应的能力。与PB2-AUG起始密码子位点互补的脂质体包裹型S-ODN显示出高度抑制作用。因此，在甲型流感病毒感染的小鼠模型中检测了S-ODN-PB2-AUG和PA-AUG的抗病毒效果。静脉注射PB2-AUG寡聚物显著延长了平均存活天数（MDS），并以剂量依赖方式提高了存活率。