Karacostas V, Nagashima K, Gonda M A, Moss B
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1989 Nov;86(22):8964-7. doi: 10.1073/pnas.86.22.8964.
Infectious retrovirus particles consist of a core structure containing RNA and gag-pol polypeptides surrounded by a lipid membrane studded with env proteins. A recombinant vaccinia virus was designed to express the entire gag-pol precursor protein of the human immunodeficiency virus type 1. Synthesis and processing of gag proteins occurred in mammalian cells infected with this live recombinant virus, and reverse transcriptase was detected largely in the medium. Electron micrographs revealed immature retrovirus-like particles budding from the plasma membrane and extracellular particles with morphological characteristics of immature and mature human immunodeficiency virus. The latter contained functional reverse transcriptase as well as processed p24 and p17 gag polypeptides. Thus, assembly and maturation of human immunodeficiency virus-like particles can occur in the absence of either infectious RNA molecules or env proteins. The production of noninfectious virus-like particles by expression vectors should be useful for biochemical studies and could provide a safe source of material for the development of vaccines.
传染性逆转录病毒颗粒由一个核心结构组成,该核心结构包含RNA和gag-pol多肽,周围是镶嵌有env蛋白的脂质膜。设计了一种重组痘苗病毒来表达人类免疫缺陷病毒1型的整个gag-pol前体蛋白。gag蛋白的合成和加工发生在感染这种活重组病毒的哺乳动物细胞中,并且逆转录酶主要在培养基中被检测到。电子显微镜照片显示有未成熟的类逆转录病毒颗粒从质膜上出芽,以及具有未成熟和成熟人类免疫缺陷病毒形态特征的细胞外颗粒。后者含有功能性逆转录酶以及加工后的p24和p17 gag多肽。因此,人类免疫缺陷病毒样颗粒的组装和成熟可以在没有传染性RNA分子或env蛋白的情况下发生。通过表达载体生产无感染性的病毒样颗粒应有助于生化研究,并可为疫苗开发提供安全的材料来源。