National Reference Center for AIDS, Department of Microbiology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Virol J. 2010 Oct 4;7:259. doi: 10.1186/1743-422X-7-259.
Multiple HIV-1 intersubtype recombinants have been identified in human populations. Previous studies from our lab group have shown that the epidemic in Argentina is characterized by the high prevalence of a circulating recombinant form, CRF12_BF, and many related BF recombinant forms. In these genomic structures a recombination breakpoint frequently involved the vpu coding region. Due to the scarce knowledge of Vpu participation in the virion release process and its impact on pathogenesis and of the functional capacities of intersubtype recombinant Vpu proteins, the aim of this work was to perform a comparative analysis on virion release capacity and relative replication capacity among viral variants harboring either a BF recombinant Vpu or a subtype B Vpu.
Our results showed that BF recombinant Vpu was associated to an increased viral particles production when compared to WT B variant in tetherin-expressing cell lines. This observation was tested in the context of a competition assay between the above mentioned variants. The results showed that the replication of the BF Vpu-harboring variant was more efficient in cell cultures than subtype B, reaching a higher frequency in the viral population in a short period of time.
This study showed that as a result of intersubtype recombination, a structurally re-organized HIV-1 Vpu has an improved in vitro capacity of enhancing viral replication, and provides evidence of the changes occurring in this protein function that could play an important role in the successful spread of intersubtype recombinant variants.
在人类群体中已经发现了多种 HIV-1 亚型重组体。我们实验室小组的先前研究表明，阿根廷的流行情况以高流行循环重组形式 CRF12_BF 和许多相关 BF 重组形式为特征。在这些基因组结构中，重组断点经常涉及 vpu 编码区。由于对 Vpu 在病毒粒子释放过程中的参与及其对发病机制和亚型间重组 Vpu 蛋白的功能能力的了解甚少，因此本工作的目的是对携带 BF 重组 Vpu 或亚型 B Vpu 的病毒变体的病毒粒子释放能力和相对复制能力进行比较分析。
我们的结果表明，与表达 tetherin 的细胞系中的 WT B 变体相比，BF 重组 Vpu 与病毒粒子产生的增加有关。在上述变体之间的竞争测定中对该观察结果进行了测试。结果表明，BF Vpu 携带变体的复制在细胞培养物中比亚型 B 更有效，在短时间内可在病毒群体中达到更高的频率。
这项研究表明，由于亚型间重组，结构上重新组织的 HIV-1 Vpu 增强了体外病毒复制的能力，并为该蛋白功能发生的变化提供了证据，这可能在成功传播亚型间重组变体中发挥重要作用。
