Matrix蛋白和G蛋白双位点突变型水泡性口炎病毒的构建及生物学活性观察

摘要

重组水泡性口炎病毒(Vesiclar stomatitis virs,VSV)是一种具有良好应用前景的病毒载体,可应用于制备疫苗和治疗肿瘤,但该载体仍存在安全性问题,高剂量注射实验动物可导致产生神经毒性.为减低乃至去除野生型VSV的致病性,作者针对VSV毒力因子,构建了Matrix蛋白和G蛋白双位点突变型重组VSV,该病毒敲除了原来Matrix蛋白的第51位精氨酸和G蛋白C末端的28个氨基酸.相比野生型VSV,新病毒的致病性显著降低.试验也证实这个致弱的病毒是由于2种不同弱化机理共同作用所致,即Ⅰ型干扰素作用和复制能力减低.新型VSV病毒载体有希望成为一个更安全、有效的疫苗载体.%Recombinant Vesiclar stomatitis virs (VSV) is an ideal viral vector for vaccine and virotherapy,however, there still exists toxicities in VSV vector. Animals exhibited neurotoxicity when injected with high dose of VSV. In order to decrease the pathogenesis by wild- typed VSV,recombinant VSV aiming at its virulent factors was developed, which included deletion of methionine 51 in matrix protein and truncation of 28 amino acids at carboxyl terminal of G protein. In comparison with wild-typed VSV,VSV△ M51-G△ 28-GFP indicated significant attenuation not only in vitro but in vivo as well. The attenuation was proved based on two different mechanisms,including type Ⅰ interferon inhibition and viral replication shortage. This novel VSV can be a promising vector for both vaccine and tumor treatment.