Kohoutová Zdena, Rumlová Michaela, Andreánsky Martin, Sakalian Michael, Hunter Eric, Pichová Iva, Ruml Tomás
Department of Biochemistry and Microbiology and the Center for Integrated Genomics, Institute of Chemical Technology, Prague, Czech Republic.
Virology. 2009 Feb 5;384(1):59-68. doi: 10.1016/j.virol.2008.10.048. Epub 2008 Dec 4.
Most retroviruses employ a frameshift mechanism during polyprotein synthesis to balance appropriate ratios of structural proteins and enzymes. To investigate the requirements for individual precursors in retrovirus assembly, we modified the polyprotein repertoire of Mason-Pfizer monkey virus (M-PMV) by mutating the frameshift sites to imitate the polyprotein organization of Rous sarcoma virus (Gag-Pro and Gag-Pro-Pol) or Human immunodeficiency virus (Gag and Gag-Pro-Pol). For the "Rous-like" virus, assembly was impaired with no incorporation of Gag-Pro-Pol into particles and for the "HIV-like" virus an altered morphogenesis was observed. A mutant expressing Gag and Gag-Pro polyproteins and lacking Gag-Pro-Pol assembled intracellular particles at a level similar to the wild-type. Gag-Pro-Pol polyprotein alone neither formed immature particles nor processed the precursor. All the mutants were non-infectious except the "HIV-like", which retained fractional infectivity.
大多数逆转录病毒在多聚蛋白合成过程中采用移码机制，以平衡结构蛋白和酶的适当比例。为了研究逆转录病毒组装中各个前体的需求，我们通过突变移码位点来模仿劳斯肉瘤病毒（Gag-Pro和Gag-Pro-Pol）或人类免疫缺陷病毒（Gag和Gag-Pro-Pol）的多聚蛋白组织，从而改变了猴空泡病毒（M-PMV）的多聚蛋白组成。对于“劳斯样”病毒，组装受损，Gag-Pro-Pol未掺入颗粒中；对于“HIV样”病毒，则观察到形态发生改变。一个表达Gag和Gag-Pro多聚蛋白而缺乏Gag-Pro-Pol的突变体在细胞内组装颗粒的水平与野生型相似。单独的Gag-Pro-Pol多聚蛋白既不形成未成熟颗粒，也不加工前体。除了保留部分感染性的“HIV样”病毒外，所有突变体均无感染性。
