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在原代淋巴细胞中产生的1型人类免疫缺陷病毒vif突变体的异常Gag蛋白组成。

Aberrant Gag protein composition of a human immunodeficiency virus type 1 vif mutant produced in primary lymphocytes.

作者信息

Simm M, Shahabuddin M, Chao W, Allan J S, Volsky D J

机构信息

Molecular Virology Laboratory, St. Luke's-Roosevelt Hospital Center and College of Physicians & Surgeons, Columbia University, New York, New York 10019, USA.

出版信息

J Virol. 1995 Jul;69(7):4582-6. doi: 10.1128/JVI.69.7.4582-4586.1995.

Abstract

Productive, spreading infection of peripheral blood lymphocytes (PBL) with human immunodeficiency virus type 1 (HIV-1) requires the viral protein Vif. To study the requirement for vif in this system, we infected PBL with a phenotypically complemented HIV-1 clone mutated in vif. Progeny virus was produced which was noninfectious in PBL but replicated in SupT1 cells. Analysis of metabolically labeled proteins of sedimentable extracellular particles made in PBL by radioimmunoprecipitation with either serum from a patient with AIDS or a monoclonal antibody reactive with HIV-1 Gag proteins revealed that vif-negative but not wild-type particles carry higher levels of p55, p41, and p38 Gag-specific proteins compared with those of p24. Similar results were obtained with sucrose-purified virions. Our data indicate that vif plays a role in Gag protein processing or in incorporation of processed Gag products into mature virions. The presence of unprocessed precursor Gag polyprotein (Pr55gag) and other Gag processing intermediates in PBL-derived vif-negative extracellular particles may contribute to the reduced infectivity of this virus.

摘要

1型人类免疫缺陷病毒(HIV-1)对外周血淋巴细胞(PBL)进行有效的、扩散性感染需要病毒蛋白Vif。为了研究该系统中对vif的需求,我们用在vif中发生突变的表型互补HIV-1克隆感染PBL。产生了子代病毒,其在PBL中无感染性,但能在SupT1细胞中复制。用来自艾滋病患者的血清或与HIV-1 Gag蛋白反应的单克隆抗体通过放射免疫沉淀分析PBL中产生的可沉降细胞外颗粒的代谢标记蛋白,结果显示,与p24相比,vif阴性而非野生型颗粒携带更高水平的p55、p4​​1和p38 Gag特异性蛋白。用蔗糖纯化的病毒体也得到了类似结果。我们的数据表明,vif在Gag蛋白加工或加工后的Gag产物掺入成熟病毒体中发挥作用。PBL来源的vif阴性细胞外颗粒中未加工的前体Gag多蛋白(Pr55gag)和其他Gag加工中间体的存在可能导致该病毒的感染性降低。

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