Nayak Ramnath, Pintel David J
Department of Molecular Microbiology and Immunology, University of Missouri-Columbia, 1201 E. Rollins Road, Columbia, MO 65211-7310, USA.
J Virol. 2007 Mar;81(5):2205-12. doi: 10.1128/JVI.02312-06. Epub 2006 Dec 13.
Full replication of adeno-associated virus type 5 (AAV5) is sustained by adenovirus type 5 (Ad5) helper functions E1a, E1b, E2a, E4Orf6, and virus-associated (VA) RNA; however, their combined net enhancement of AAV5 replication was comprised of both positive and negative individual effects. Although Ad5 E4Orf6 was required for AAV5 genomic DNA replication, it also functioned together with E1b to degrade de novo-expressed, preassembled AAV5 capsid proteins and Rep52 in a proteosome-dependent manner. VA RNA enhanced accumulation of AAV5 protein, overcoming the degradative effects of E4Orf6, and was thus required to restore adequate amounts of AAV5 proteins necessary to achieve efficient virus production.
5型腺相关病毒(AAV5)的完全复制由5型腺病毒(Ad5)的辅助功能E1a、E1b、E2a、E4Orf6和病毒相关(VA)RNA维持;然而,它们对AAV5复制的综合净增强作用包括正向和负向的个体效应。虽然Ad5 E4Orf6是AAV5基因组DNA复制所必需的,但它也与E1b共同作用,以蛋白酶体依赖的方式降解新表达的、预组装的AAV5衣壳蛋白和Rep52。VA RNA增强了AAV5蛋白的积累,克服了E4Orf6的降解作用,因此是恢复高效病毒生产所需的足够数量的AAV5蛋白所必需的。