Forshey Brett M, von Schwedler Uta, Sundquist Wesley I, Aiken Christopher
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
J Virol. 2002 Jun;76(11):5667-77. doi: 10.1128/jvi.76.11.5667-5677.2002.
Virions of human immunodeficiency virus type 1 (HIV-1) and other lentiviruses contain conical cores consisting of a protein shell composed of the viral capsid protein (CA) surrounding an internal viral ribonucleoprotein complex. Although genetic studies have implicated CA in both early and late stages of the virus replication cycle, the mechanism of core disassembly following penetration of target cells remains undefined. Using quantitative assays for analyzing HIV-1 core stability in vitro, we identified point mutations in CA that either reduce or increase the stability of the HIV-1 core without impairing conical core formation in virions. Alterations in core stability resulted in severely attenuated HIV-1 replication and impaired reverse transcription in target cells with only minimal effects on viral DNA synthesis in permeabilized virions in vitro. We conclude that formation of a viral core of optimal stability is a prerequisite for efficient HIV-1 infection and suggest that disassembly of the HIV-1 core is a regulated step in infection that may be an attractive target for pharmacologic intervention.
1型人类免疫缺陷病毒（HIV-1）及其他慢病毒的病毒粒子含有锥形核心，该核心由病毒衣壳蛋白（CA）构成的蛋白质外壳组成，围绕着内部的病毒核糖核蛋白复合体。尽管遗传学研究表明CA在病毒复制周期的早期和晚期均发挥作用，但靶细胞穿透后核心解体的机制仍不明确。通过定量分析HIV-1核心在体外的稳定性，我们在CA中鉴定出点突变，这些突变要么降低要么增加HIV-1核心的稳定性，而不影响病毒粒子中锥形核心的形成。核心稳定性的改变导致HIV-1复制严重减弱，靶细胞中的逆转录受损，而对体外通透化病毒粒子中的病毒DNA合成影响极小。我们得出结论，形成具有最佳稳定性的病毒核心是HIV-1有效感染的先决条件，并表明HIV-1核心的解体是感染过程中的一个受调控步骤，可能是药物干预的一个有吸引力的靶点。
