Aldrovandi G M, Zack J A
Department of Medicine, UCLA School of Medicine, USA.
J Virol. 1996 Mar;70(3):1505-11. doi: 10.1128/JVI.70.3.1505-1511.1996.
The functional roles of the human immunodeficiency virus type 1 (HIV-1) accessory genes (nef, vpr, vpu, and vif) are as yet unclear. Using the SCID-hu model system, we have examined the infectivity, replicative capacity, and pathogenicity of strains of the molecular clone HIV-1NL4-3 that contain deletion mutations in these individual accessory genes. We determined that deletion of these genes had differential effects on both infectivity and pathogenicity. Deletion of vpr had little or no effect on viral infectivity, replication, and pathogenicity; however, deletion of vpu or vif had a significant effect on infectivity and moderate effects on pathogenicity. nef-minus strains were the most attenuated in this system, demonstrating significantly lower levels of infectivity and pathogenicity. However, deletion of these individual genes attenuated but did not abrogate the pathogenic properties of HIV-1. Mutant viruses still retained the ability to induce thymocyte depletion to various degrees if implants were infected with higher doses of virus or observed for longer periods of time. The relative contributions of these genes to in vivo pathogenic potential should be taken into consideration when one is contemplating a live attenuated vaccine for HIV-1.
人类免疫缺陷病毒1型（HIV-1）辅助基因（nef、vpr、vpu和vif）的功能作用尚不清楚。利用重症联合免疫缺陷（SCID）-人模型系统，我们研究了在这些单个辅助基因中含有缺失突变的分子克隆HIV-1NL4-3毒株的感染性、复制能力和致病性。我们确定这些基因的缺失对感染性和致病性都有不同的影响。vpr的缺失对病毒感染性、复制和致病性几乎没有影响；然而，vpu或vif的缺失对感染性有显著影响，对致病性有中等影响。在该系统中，缺失nef的毒株减毒程度最高，其感染性和致病性水平显著降低。然而，这些单个基因的缺失使HIV-1的致病特性减弱但并未消除。如果植入物用更高剂量的病毒感染或观察更长时间，突变病毒仍保留在不同程度上诱导胸腺细胞耗竭的能力。在考虑开发HIV-1减毒活疫苗时，应考虑这些基因对体内致病潜力的相对贡献。
