Genetic bases of the temperature-sensitive phenotype of a master donor virus used in live attenuated influenza vaccines: A/Leningrad/134/17/57 (H2N2)
Genetic bases of the temperature-sensitive phenotype of a master donor virus used in live attenuated influenza vaccines: A/Leningrad/134/17/57 (H2N2)
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DOI：
10.1016/j.virol.2011.01.004
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发表时间：
2011-04-10
期刊：
影响因子：
3.7
通讯作者：
Donis, Ruben O.
中科院分区：
文献类型：
--
作者：
Isakova-Sivak, Irina;Chen, Li-Mei;Donis, Ruben O.
以冷适应A/Leningrad/134/17/57(H_2N_2)(CaLen17)主供体病毒(MDV)为基础的A型减毒活疫苗几十年来在俄罗斯被成功地用于控制流感。疫苗病毒包括来自流行病毒的血凝素和神经氨酸酶基因，以及来自MDV的其余六个基因。后者可分为温度敏感型(Ts)和衰减型(att型)。疫苗病毒的ts表型是毒力减弱的关键生物学决定因素。我们建立了MDV caLen17的质粒型反向遗传系统，以研究其ts表型的遗传基础。聚合酶蛋白P81和Pb2的突变在MDV caLen17的ts表型中起着至关重要的作用。此外，我们还发现，caLen17特异的ts突变可以将ts表型传递给发散的PR8病毒，这表明将ts表型转移到新的疫苗开发中是可行的。由爱思唯尔公司出版。
Trivalent live attenuated influenza vaccines whose type A components are based on cold-adapted A/Leningrad/134/17/57 (H2N2) (caLen17) master donor virus (MDV) have been successfully used in Russia for decades to control influenza. The vaccine virus comprises hemagglutinin and neuraminidase genes from the circulating viruses and the remaining six genes from the MDV. The latter confer temperature-sensitive (ts) and attenuated (att) phenotypes. The ts phenotype of the vaccine virus is a critical biological determinant of attenuation of virulence. We developed a plasmid-based reverse genetics system for MDV caLen17 to study the genetic basis of its ts phenotype. Mutations in the polymerase proteins P81 and PB2 played a crucial role in the ts phenotype of MDV caLen17. In addition, we show that caLen17-specific ts mutations could impart the ts phenotype to the divergent PR8 virus, suggesting the feasibility of transferring the ts phenotype to new viruses of interest for vaccine development. Published by Elsevier Inc.