Optimized Infectivity of the Cell-Free Single-Cycle Human Immunodeficiency Viruses Type 1 (HIV-1) and Its Restriction by Host Cells.
Optimized Infectivity of the Cell-Free Single-Cycle Human Immunodeficiency Viruses Type 1 (HIV-1) and Its Restriction by Host Cells.
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DOI：
10.1371/journal.pone.0067170
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Cheng W
中科院分区：
文献类型：
--
作者：
Kim JH;Song H;Austin JL;Cheng W
逆转录病毒如HIV-1在血浆或培养基中的感染性通常小于0.1%，其机制尚未完全了解。其中一个可能的解释是病毒库中可能存在大量缺陷病毒体，这限制了HIV病毒体的明显感染性。为了验证这一假设，我们改变了用于产生单循环HIV-1病毒体的培养条件。在这些培养变量中，病毒体收获时间、转染后培养基更换和包膜质粒输入都可以通过减少缺陷病毒体的数量来提高HIV-1的感染性。转染后18-24小时而不是48小时的收获时间，以及转染后6小时更换培养基都提高了病毒感染性。在转染过程中的包膜质粒输入的最佳数量也found. Collectively，这些条件增加了HIV-1病毒粒子的感染性的7倍相比，正常报道的值在TZM-BL指示细胞系。这些条件还增加了CD 4 + T细胞中HIV-1的感染性，这表明这些条件通过增加病毒库的内在感染性来发挥作用。然而，与宿主细胞对HIV感染的影响相比，这些对病毒粒子感染性的改善是微不足道的，即使对于最优化的病毒，其也可以将表观感染性降低19倍。这些结果表明，HIV-1病毒粒子的感染性可以通过减少缺陷病毒粒子的数量来优化;然而，病毒-细胞相互作用可能对HIV-1感染性构成主要障碍。
The infectivity of retroviruses such as HIV-1 in plasma or cultured media is less than 0.1% in general, the mechanisms of which are not yet fully understood. One possible explanation among others is the potential presence of large numbers of defective virions in a virus pool, which limits the apparent infectivity of HIV virions. To test this hypothesis, we have varied the culture conditions used to generate single-cycle HIV-1 virions. Among these culture variables, virion harvest time, media change after transfection, and envelope plasmid input can all improve HIV-1 infectivity by reducing the number of defective virions. A harvest time of 18–24 hours post transfection as opposed to 48 hours, and a media change six hours post transfection both improve viral infectivity. An optimal quantity of envelope plasmid input during transfection was also found. Collectively, these conditions increased the infectivity of HIV-1 virions by sevenfold compared to normally reported values in TZM-bl indicator cell lines. These conditions also increased the infectivity of HIV-1 in CD4+ T cells, suggesting that these conditions work by increasing the intrinsic infectivity of a virus pool. Nevertheless, these improvements on virion infectivity were marginal compared to the impact of host cells on HIV infection, which can decrease the apparent infectivity by 19-fold even for the most optimized viruses. These results suggest that the infectivity of HIV-1 virions can be optimized by reducing the number of defective virions; however, viral-cell interactions may pose a major barrier for HIV-1 infectivity.
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