针对PB1 mRNA的核酶对甲型流感病毒复制的抑制作用。

Inhibition of influenza A virus reproduction by a ribozyme targeted against PB1 mRNA.

作者信息

Lazarev V N, Shmarov M M, Zakhartchouk A N, Yurov G K, Misurina O U, Akopian T A, Grinenko N F, Grodnitskaya N G, Kaverin N V, Naroditsky B S

机构信息

Institute of Agricultural Biotechnology, Russian Academy of Agricultural Science, Moscow.

出版信息

Antiviral Res. 1999 May;42(1):47-57. doi: 10.1016/s0166-3542(99)00015-7.

DOI:10.1016/s0166-3542(99)00015-7

PMID:10333142

Abstract

A ribozyme gene directed at a specific cleavage of mRNA coding for PB1 protein, a component of RNA-dependent RNA-polymerase of influenza A virus, was constructed. The avian adenovirus CELO virus-associated RNA (VA RNA CELO) promoter and human cytomegalovirus (CMV) promoter were used for the permanent expression of the ribozyme in cell lines. The cells were infected with influenza A virus strains A/Singapore/1/57 and A/WSN/33, and the suppression of the virus reproduction and virus-specific protein synthesis was measured. The maximal level of the inhibition of virus reproduction as compared to the reproduction in non-transformed cells was 93.5%. Defective recombinant adenoviruses were constructed carrying the genes of functional and non-functional ribozymes under the control of human cytomegalovirus (CMV) promoter. The reproduction of A/WSN/33 virus in CV-1 cells preinfected with recombinant adenoviruses was shown to be suppressed.

摘要

构建了一种针对甲型流感病毒依赖RNA的RNA聚合酶组分PB1蛋白编码mRNA特定切割的核酶基因。禽腺病毒CELO病毒相关RNA（VA RNA CELO）启动子和人巨细胞病毒（CMV）启动子用于核酶在细胞系中的永久表达。用甲型流感病毒株A/新加坡/1/57和A/WSN/33感染细胞，并测定病毒繁殖和病毒特异性蛋白合成的抑制情况。与未转化细胞中的繁殖相比，病毒繁殖的最大抑制水平为93.5%。构建了在人巨细胞病毒（CMV）启动子控制下携带功能性和非功能性核酶基因的缺陷型重组腺病毒。结果显示，重组腺病毒预感染的CV-1细胞中A/WSN/33病毒的繁殖受到抑制。