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首页> 外文期刊>AIDS Research and Human Retroviruses >Glycosylphosphatidylinositol Anchor Deficiency Attenuates the Production of Infectious HIV-1 and Renders Virions Sensitive to Complement Attack
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Glycosylphosphatidylinositol Anchor Deficiency Attenuates the Production of Infectious HIV-1 and Renders Virions Sensitive to Complement Attack

机译：糖基磷脂酰肌醇锚固缺乏症减弱了感染性HIV-1的产生，并提供了对补体攻击敏感的病毒颗粒。

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Human immunodeficiency virus type 1 (HIV-1) escapes complement-mediated lysis (CML) by incorporating host regulators of complement activation (RCA) into its envelope. CD59, a key member of RCA, is incorporated into HIV-1 virions at levels that protect against CML. Since CD59 is a glycosylphosphatidylinositol-anchored protein (GPI-AP), we used GPI anchor-deficient Jurkat cells (Jurkat-7) that express intracellular CD59, but not surface CD59, to study the molecular mechanisms underlying CD59 incorporation into HIV-1 virions and the role of host proteins in virus replication. Compared to Jurkat cells, Jurkat-7 cells were less supportive to HIV-1 replication and more sensitive to CML. Jurkat-7 cells exhibited similar capacities of HIV-1 binding and entry to Jurkat cells, but were less supportive to viral RNA and DNA biosynthesis as infected Jurkat-7 cells produced reduced amounts of HIV-1 RNA and DNA. HIV-1 virions produced from Jurkat-7 cells were CD59 negative, suggesting that viral particles acquire CD59, and probably other host proteins, from the cell membrane rather than intracellular compartments. As a result, CD59-negative virions were sensitive to CML. Strikingly, these virions exhibited reduced activity of virus binding and were less infectious, implicating that GPI-APs may be also important in ensuring the integrity of HIV-1 particles. Transient expression of the PIG-A gene restored CD59 expression on the surface of Jurkat-7 cells. After HIV-1 infection, the restored CD59 was colocalized with viral envelope glycoprotein gp120/gp41 within lipid rafts, which is identical to that on infected Jurkat cells. Thus, HIV-1 virions acquire RCA from the cell surface, likely lipid rafts, to escape CML and ensure viral infectivity.
机译：人类免疫缺陷病毒1型（HIV-1）通过将宿主补体激活调节剂（RCA）掺入其包膜中而逃脱了补体介导的裂解（CML）。 CD59是RCA的重要成员，它以防止CML的水平被掺入HIV-1病毒粒子中。由于CD59是糖基磷脂酰肌醇固定蛋白（GPI-AP），因此我们使用表达细胞内CD59但不表达表面CD59的GPI锚定缺陷Jurkat细胞（Jurkat-7），研究CD59掺入HIV-1病毒颗粒的分子机制。以及宿主蛋白在病毒复制中的作用。与Jurkat细胞相比，Jurkat-7细胞对HIV-1复制的支持较少，对CML更敏感。 Jurkat-7细胞显示出与HIV-1结合和进入Jurkat细胞相似的能力，但由于感染的Jurkat-7细胞产生的HIV-1 RNA和DNA数量减少，因此对病毒RNA和DNA生物合成的支持较少。从Jurkat-7细胞产生的HIV-1病毒颗粒CD59阴性，表明病毒颗粒从细胞膜而不是细胞内区室获得CD59，可能还有其他宿主蛋白。结果，CD59阴性病毒粒子对CML敏感。令人惊讶的是，这些病毒体显示出降低的病毒结合活性，并且传染性较小，这暗示GPI-AP在确保HIV-1颗粒的完整性方面也可能很重要。 PIG-A基因的瞬时表达恢复了Jurkat-7细胞表面的CD59表达。 HIV-1感染后，恢复的CD59与脂质筏中的病毒包膜糖蛋白gp120 / gp41共定位，这与受感染的Jurkat细胞相同。因此，HIV-1病毒粒子从细胞表面获得RCA，可能是脂筏，从而逃脱CML并确保病毒感染性。

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