A highly pathogenic simian/human immunodeficiency virus effectively produces infectious virions compared with a less pathogenic virus in cell culture.
A highly pathogenic simian/human immunodeficiency virus effectively produces infectious virions compared with a less pathogenic virus in cell culture.
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DOI：
10.1186/s12976-017-0055-8
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发表时间：
2017-04-21
影响因子：
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通讯作者：
Iwami S
中科院分区：
文献类型：
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作者：
Iwanami S;Kakizoe Y;Morita S;Miura T;Nakaoka S;Iwami S
人类免疫缺陷病毒（HIV）的宿主范围很窄。因此，由于缺乏合适的动物模型系统，分析HIV-1的体内发病机制受到限制。为了克服这一点，嵌合猿和人类免疫缺陷病毒（SHIV），编码HIV-1的Env和感染猕猴已被开发和用于研究体内的HIV-1的致病性。到目前为止，我们有许多SHIV毒株在猕猴实验中显示出不同的致病性。然而，SHIV感染的动态方面尚未得到很好的理解。为了充分了解SHIV的动态特性，我们集中在两个代表性菌株-高致病性SHIV，SHIV-KS 661和致病性较低的SHIV，SHIV-#64-并测量细胞培养实验数据的时间过程。我们用SHIV-KS 661和-#64感染HSC-F，并每天测量Nef阴性（靶）和Nef阳性（感染的）HSC-F细胞的浓度、总病毒载量和感染性病毒载量，持续9天。在两种不同的感染多重性下重复实验，并将先前开发的合并感染性和非感染性病毒的数学模型同时拟合到每种菌株的完整数据集，以表征这两种菌株的感染动力学。我们定量了SHIV-KS 661和-#64的病毒学指标，包括病毒爆发大小和基本繁殖数。比较总病毒和感染性病毒的爆发大小（分别为病毒RNA拷贝和TCID 50），我们发现SHIV-KS 661和-#64的感染性病毒爆发大小之间存在统计学显著差异，而总病毒爆发大小之间没有显著差异。此外，我们的分析显示，在整个感染过程中，所产生的SHIV-KS 661病毒中感染性病毒的分数（定义为感染性病毒载量（TCID 50/ml）除以总病毒载量（RNA拷贝/ml））比SHIV-#64高10倍以上（即，9天）。综上所述，我们得出结论，高致病性SHIV比低致病性SHIV在细胞培养中更有效地产生感染性病毒体。本文的在线版本（doi：10.1186/s12976-017-0055-8）包含补充材料，可供授权用户使用。
The host range of human immunodeficiency virus (HIV) is quite narrow. Therefore, analyzing HIV-1 pathogenesis in vivo has been limited owing to lack of appropriate animal model systems. To overcome this, chimeric simian and human immunodeficiency viruses (SHIVs) that encode HIV-1 Env and are infectious to macaques have been developed and used to investigate the pathogenicity of HIV-1 in vivo. So far, we have many SHIV strains that show different pathogenesis in macaque experiments. However, dynamic aspects of SHIV infection have not been well understood. To fully understand the dynamic properties of SHIVs, we focused on two representative strains—the highly pathogenic SHIV, SHIV-KS661, and the less pathogenic SHIV, SHIV-#64—and measured the time-course of experimental data in cell culture. We infected HSC-F with SHIV-KS661 and -#64 and measured the concentration of Nef-negative (target) and Nef-positive (infected) HSC-F cells, the total viral load, and the infectious viral load daily for 9 days. The experiments were repeated at two different multiplicities of infection, and a previously developed mathematical model incorporating the infectious and non-infectious viruses was fitted to the full dataset of each strain simultaneously to characterize the infection dynamics of these two strains. We quantified virological indices including virus burst sizes and basic reproduction number of both SHIV-KS661 and -#64. Comparing the burst size of total and infectious viruses (viral RNA copies and TCID50, respectively), we found that there was a statistically significant difference between the infectious virus burst size of SHIV-KS661 and -#64, while there was no significant difference between the total virus burst size. Furthermore, our analyses showed that the fraction of infectious virus among the produced SHIV-KS661 viruses, which is defined as the infectious viral load (TCID50/ml) divided by the total viral load (RNA copies/ml), is more than 10-fold higher than that of SHIV-#64 during overall infection (i.e., for 9 days). Taken together, we conclude that the highly pathogenic SHIV produces infectious virions more effectively than the less pathogenic SHIV in cell culture. The online version of this article (doi:10.1186/s12976-017-0055-8) contains supplementary material, which is available to authorized users.