HIV-1 Vpr does not inhibit CTL-mediated apoptosis of HIV-1 infected cells.
HIV-1 Vpr does not inhibit CTL-mediated apoptosis of HIV-1 infected cells.
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HIV-1 Vpr 不会抑制 CTL 介导的 HIV-1 感染细胞凋亡。
DOI：
10.1006/viro.2001.1294
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发表时间：
2002
期刊：
影响因子：
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通讯作者：
Bartz,StevenR
中科院分区：
文献类型：
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作者：
Lewinsohn,DeborahA;Lines,Rebecca;Lewinsohn,DavidM;Riddell,StanleyR;Greenberg,PhilipD;Emerman,Michael;Bartz,StevenR
HIV-1感染者对HIV抗原产生强大的CTL反应，但HIV-1能够逃避这种宿主反应并成功复制。逃避的机制尚未完全确定，但有人认为包括感染细胞对ctl介导的凋亡的抗性。HIV-1 Vpr蛋白通过间接抑制细胞周期蛋白B/p34cdc2激酶的激活诱导G2阻滞。颗粒酶B， ctl诱导细胞凋亡的主要介质，提前激活了相同的激酶复合物。因此，我们评估了HIV-1感染细胞对ctl介导的凋亡的易感性，以确定Vpr的表达是否保护感染细胞免受ctl诱导的凋亡。抗原特异性CD8+CTL能够诱导HIV-1感染细胞和与CTL表位对应的肽标记的细胞凋亡，并且具有相同的效率。这表明HIV-1 Vpr和任何其他HIV蛋白都不能直接抑制CTL效应的功能。此外，我们证实HIV-1 Nef能够对受感染细胞的CTL识别提供部分保护。因此，CTL无法控制HIV-1感染可能不是由于CTL介导的细胞凋亡的直接抑制。
HIV-1 infected persons develop a robust CTL response to HIV antigens, yet HIV-1 is able to evade this host response and successfully replicate. The mechanism(s) of evasion is not completely defined but has been suggested to include resistance of infected cells to CTL-mediated apoptosis. The HIV-1 Vpr protein induces G2 arrest by indirectly inhibiting activation of cyclin B/p34cdc2 kinase. Granzyme B, the principle mediator of CTL-induced apoptosis, prematurely activates this same kinase complex. Therefore, we assessed the susceptibility of HIV-1 infected cells to CTL-mediated apoptosis to determine whether the expression of Vpr protected the infected cells from CTL-induced apoptosis. Antigen-specific CD8+CTL were able to induce apoptosis in HIV-1 infected cells and cells labeled with peptide corresponding to the CTL epitope with equivalent efficiency. This demonstrates that neither HIV-1 Vpr nor any other HIV protein directly inhibits CTL effector functions. Furthermore, we confirm that HIV-1 Nef is able to provide partial protection from CTL recognition of infected cells. Thus, the inability of CTL to control HIV-1 infection is likely not due to direct inhibition of CTL-mediated apoptosis.