Cytopathic killing of peripheral blood CD4(+) T lymphocytes by human immunodeficiency virus type 1 appears necrotic rather than apoptotic and does not require env.
Cytopathic killing of peripheral blood CD4(+) T lymphocytes by human immunodeficiency virus type 1 appears necrotic rather than apoptotic and does not require env.
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人类免疫缺陷病毒 1 型对外周血 CD4(+) T 淋巴细胞的细胞病变杀伤表现为坏死而不是凋亡，并且不需要 env。
DOI：
10.1128/jvi.76.10.5082-5093.2002
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发表时间：
2002
影响因子：
5.4
通讯作者：
Bolton,DianeL
中科院分区：
文献类型：
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作者：
Lenardo,MichaelJ;Angleman,SaraB;Bounkeua,Viengngeun;Dimas,Joseph;Duvall,MelodyG;Graubard,MosesB;Hornung,Felicita;Selkirk,MarianneC;Speirs,ChristinaK;Trageser,Carol;Orenstein,JanO;Bolton,DianeL
艾滋病发病机制的一个重要尚未解决的问题是人类免疫缺陷病毒（HIV）诱导CD4+ t淋巴细胞破坏的机制。我们在这里表明，HIV-1型（HIV-1）对外周血CD4+T淋巴细胞产生深刻的细胞病变作用，类似于坏死而不是凋亡。在实验室适应株和原代分离株中均发现坏死细胞病理学。我们仔细研究了env的作用，它以前被认为与HIV细胞病变有关。用完整或突变的编码区构建具有相同感染性的HIV-1基因库，并用水泡性口炎病毒（VSV-G）的糖蛋白进行假型，这样HIV包膜就不会对感染造成限制。感染的Jurkat T细胞无论是否完整都死亡；然而，这种表达明显加速了死亡。蛋白酶抑制剂阻断了加速死亡，表明这是由于新产生的病毒inenv+培养物的再感染。因此，我们发现CD4loJurkat细胞的动力学没有差异。在高度感染的外周血T细胞中，HIV-1的v+和v -组同样发生深度坏死。我们还发现，HIV-1细胞致病性并没有因为nef的缺失而减弱。然而，用绿色荧光蛋白替代天然蛋白编码序列，通过对HIV-1基因组进行互补或包装制成的病毒库具有高度传染性，但不会引起细胞病变。因此，envin主要作为一种进入功能加速细胞死亡，但在HIV-1诱导的CD4+T细胞坏死中，除了envin之外，还有一种或多种病毒功能是必不可少的。
An important unresolved issue of AIDS pathogenesis is the mechanism of human immunodeficiency virus (HIV)-induced CD4+T-lymphocyte destruction. We show here that HIV type 1 (HIV-1) exerts a profound cytopathic effect upon peripheral blood CD4+T lymphocytes that resembles necrosis rather than apoptosis. Necrotic cytopathology was found with both laboratory-adapted strains and primary isolates of HIV-1. We carefully investigated the role ofenv, which has been previously implicated in HIV cytopathicity. HIV-1 stocks with equivalent infectivity were prepared from constructs with either an intact or mutatedenvcoding region and pseudotyped with the glycoprotein of vesicular stomatitis virus (VSV-G) so that the HIV envelope was not rate-limiting for infection. Infected Jurkat T cells died whether or notenvwas intact; however, the expression ofenvaccelerated death significantly. The accelerated death was blocked by protease inhibitors, indicating that it was due to reinfection by newly produced virus inenv+cultures. Accordingly, we found no disparity in kinetics in CD4loJurkat cells. In highly infected peripheral blood T cells, profound necrosis occurred equivalently with bothenv+andenv−stocks of HIV-1. We also found that HIV-1 cytopathicity was undiminished by the absence ofnef. However, viral stocks made by complementation or packaging of HIV-1 genomes with the natural protein-coding sequences replaced by the green fluorescent protein were highly infectious but not cytopathic. Thus,envcan accelerate cell death chiefly as an entry function, but one or more viral functions other thanenvornefis essential for necrosis of CD4+T cells induced by HIV-1.