Involvement of HIV-1 protease in virus-induced cell killing
Involvement of HIV-1 protease in virus-induced cell killing
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DOI：
10.1016/j.antiviral.2004.12.008
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发表时间：
2005-04-01
影响因子：
7.6
通讯作者：
Carrasco, L
中科院分区：
文献类型：
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作者：
Ventoso, L;Navarro, J;Carrasco, L
HIV-1细胞病变株急性感染人CD4（+）细胞可导致细胞快速死亡。通过对C8166细胞进行单轮感染，研究了HIV-1蛋白酶（PR）在病毒诱导的细胞杀伤中的作用。感染24小时后HIV-1 PR抑制剂沙奎那韦的存在阻止了病毒诱导的细胞裂解。这种抑制剂仅引起感染细胞数量和hiv -1特异性蛋白表达的少量减少。此外，阻断HIV-1再感染的治疗方法，如AZT或抗cd4抗体leu3。A，对病毒诱导的细胞死亡几乎没有影响。因此，HIV-1蛋白酶的特异性抑制降低了C8166细胞的坏死和凋亡程度，使得大多数细胞在HIV-1感染中存活下来。继续用沙奎那韦治疗感染细胞导致HIV-1表达的进行性抑制；初次感染后10天未检测到病毒蛋白。值得注意的是，通过去除沙奎那韦，这些细胞中HIV-1蛋白酶的再激活触发了病毒复制和细胞裂解。这些发现可能有助于更好地了解HIV-1的发病机制，并强调病毒蛋白酶作为艾滋病治疗的关键治疗靶点的潜力。(c) 2005 Elsevier B.V.版权所有
Acute infection of human CD4(+) cells with cytopathic strains of HIV-1 causes rapid cell death. The role played by HIV-1 protease (PR) in virus-induced cell killing was investigated by subjecting C8166 cells to a single round of infection. The presence of HIV-1 PR inhibitor saquinavir from 24 h post-infection prevented virus-induced cell lysis. This inhibitor caused only a small reduction in the number of infected cells and in the expression of HIV-1-specific proteins. Moreover, treatments that block HIV-1 reinfection, Such as AZT or the anti-CD4 antibody leu3.a, exerted little effect on virus-induced cell death. Thus, the specific inhibition of HIV- I protease reduced the extent of both necrosis and apoptosis in C8166 cells such that most cells survived HIV-1 infection. Continued treatment of the infected cells with saquinavir led to the progressive Suppression of HIV-1 expression; no viral proteins being detected 10 days after primary infection. Notably, reactivation of HIV-1 protease in these cells by removing the saquinavir triggered virus replication and cell lysis. These findings may contribute towards a better understanding of HIV-1 pathogenesis, and emphasise the potential of the virus protease as a key therapeutic target in AIDS treatment. (c) 2005 Elsevier B.V. All rights reserved.