Implications of CTL-Mediated Killing of HIV-Infected Cells during the Non-Productive Stage of Infection
Implications of CTL-Mediated Killing of HIV-Infected Cells during the Non-Productive Stage of Infection
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DOI：
10.1371/journal.pone.0016468
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发表时间：
2011-02-07
期刊：
影响因子：
3.7
通讯作者：
De Boer, Rob J.
中科院分区：
文献类型：
--
作者：
Althaus, Christian L.;De Boer, Rob J.
感染HIV的患者在其血浆病毒载量的设定点水平上表现出数量级的差异。至于这种差异在多大程度上是由于这些患者的细胞毒性T淋巴细胞（CTL）反应的疗效不同造成的，目前尚不清楚。一些研究表明，hiv感染的CD4(+) T细胞在感染的产生阶段之前，即在被感染的细胞开始产生新的病毒颗粒之前的细胞内日食阶段，也存在被ctl识别的病毒表位。在这里，我们使用数学模型来研究早期杀死hiv感染细胞对病毒复制的潜在影响。我们认为，大多数ctl介导的杀伤可能发生在病毒消隐期，并且由于mhc - i下调，在后期产生病毒的细胞的杀伤可能大大降低。这种机制与一些实验观察一致，包括CD8(+) T细胞耗竭和抗逆转录病毒药物治疗。这表明ctl介导的杀伤在hiv感染细胞的非生产阶段具有潜在的重要作用。
Patients infected with HIV exhibit orders of magnitude differences in their set-point levels of the plasma viral load. As to what extent this variation is due to differences in the efficacy of the cytotoxic T lymphocyte (CTL) response in these patients is unclear. Several studies have shown that HIV-infected CD4(+) T cells also present viral epitopes that are recognized by CTLs before the productive stage of infection, i.e., during the intracellular eclipse phase before the infected cell starts to produce new viral particles. Here, we use mathematical modeling to investigate the potential impact of early killing of HIV-infected cells on viral replication. We suggest that the majority of CTL-mediated killing could occur during the viral eclipse phase, and that the killing of virus-producing cells could be substantially lower at later stages due to MHC-I-down-regulation. Such a mechanism is in agreement with several experimental observations that include CD8(+) T cell depletion and antiretroviral drug treatment. This indicates a potentially important role of CTL-mediated killing during the non-productive stage of HIV-infected cells.