Volkova Eugenia, Gorchakov Rodion, Frolov Ilya
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1019, USA.
Virology. 2006 Jan 20;344(2):315-27. doi: 10.1016/j.virol.2005.09.010. Epub 2005 Oct 18.
Alphaviruses are regarded as attractive systems for expression of heterologous genes and development of recombinant vaccines. Venezuelan equine encephalitis virus (VEE)-based vectors are particularly promising because of their specificity to lymphoid tissues and strong resistance to interferon. To improve understanding of the VEE genome packaging and optimize application of this virus as a vector, we analyzed in more detail the mechanism of packaging of the VEE-specific RNAs. The presence of the RNAs in the VEE particles during serial passaging in tissue culture was found to depend not only on the presence of packaging signal(s), but also on the ability of these RNAs to express in cis nsP1, nsP2 and nsP3 in the form of a P123 precursor. Packaging of VEE genomes into infectious virions was also found to be more efficient compared to that of Sindbis virus, in spite of lower levels of RNA replication and structural protein production.
甲病毒被认为是用于表达异源基因和开发重组疫苗的有吸引力的系统。基于委内瑞拉马脑炎病毒(VEE)的载体特别有前景,因为它们对淋巴组织具有特异性且对干扰素具有很强的抗性。为了更好地理解VEE基因组包装并优化这种病毒作为载体的应用,我们更详细地分析了VEE特异性RNA的包装机制。发现在组织培养中连续传代期间VEE颗粒中RNA的存在不仅取决于包装信号的存在,还取决于这些RNA以P123前体形式顺式表达nsP1、nsP2和nsP3的能力。尽管RNA复制水平和结构蛋白产生水平较低,但与辛德毕斯病毒相比,VEE基因组包装到感染性病毒粒子中的效率也更高。