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

In vitro and in vivo anti-influenza A virus activity of antisense oligonucleotides.
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反义寡核苷酸的体外和体内抗甲型流感病毒活性。

DOI:
10.1080/07328319908044823
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发表时间:
1999
期刊:
Nucleosides & nucleotides
影响因子:
--
通讯作者:
H. Takaku
H. Takaku
中科院分区:
--
文献类型:
--
作者:
T. Abe;T. Mizuta;S. Suzuki;T. Hatta;K. Takai;T. Yokota;H. Takaku

文献摘要

被引文献

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我们已经证明了反义硫代寡核苷酸(S-ODN)可以抑制甲型流感病毒在MDCK细胞中的复制。用MDCK细胞用四甲基偶氮唑蓝(四甲基偶氮唑蓝)比色法检测脂质体包裹的和游离的具有四个靶点(PB1、PB2、PA和NP)的反义硫代寡核苷酸对病毒诱导的细胞病变的抑制作用。与PB2-AUG起始密码子位置互补的脂质体包裹的S寡核苷酸具有很强的抑制作用。因此,我们在甲型流感病毒感染的小鼠模型上观察了S-ODN-PB2-AUG和PA-AUG的抗病毒作用。PB2-AUG齐聚物静脉注射。以剂量依赖方式显著延长小鼠平均日间存活时间(MDS),提高小鼠存活率。
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.