Rits Maarten A N, van Dort Karel A, Münk Carsten, Meijer Alexander B, Kootstra Neeltje A
Department of Clinical Viro Immunology, Sanquin Research, Landsteiner Laboratory, Amsterdam, The Netherlands.
Mol Ther. 2007 May;15(5):930-7. doi: 10.1038/mt.sj.6300091. Epub 2007 Feb 13.
Recently, the cyclophilin A (CyPA)-binding region of the HIV-1 capsid protein was identified as a viral determinant involved in the post-entry restriction in Old World monkey cells. Here, we constructed a panel of HIV-1-based lentiviral vectors (LVs) that contain either mutations in the CyPA-binding region or the CyPA-binding region of the related viruses HIV-1 group O and HIV-2. We demonstrated that amino-acid changes in the CyPA-binding region of the capsid can alter the phenotype of the virus resulting in CyPA-independent infection in human cells and non-restricted infection in simian cells. Combining these data with the available structural data, we speculate that reduced affinity of the capsid for CyPA is associated with an unrestricted infection of simian cells. In addition, we observed that primary rhesus macaque peripheral blood mononuclear cells could be transduced efficiently by the LV that contained the CyPA-binding region of HIV-2. Therefore, this LV might be very useful for long-term safety studies in large animal models like rhesus macaques.
最近，HIV-1衣壳蛋白的亲环素A（CyPA）结合区域被确定为参与旧世界猴细胞进入后限制的病毒决定因素。在此，我们构建了一组基于HIV-1的慢病毒载体（LVs），这些载体要么在CyPA结合区域有突变，要么包含相关病毒HIV-1 O组和HIV-2的CyPA结合区域。我们证明，衣壳的CyPA结合区域中的氨基酸变化可改变病毒的表型，导致在人细胞中不依赖CyPA的感染以及在猿猴细胞中的无限制感染。将这些数据与现有的结构数据相结合，我们推测衣壳对CyPA的亲和力降低与猿猴细胞的无限制感染有关。此外，我们观察到，含有HIV-2的CyPA结合区域的LV可以有效地转导原代恒河猴外周血单核细胞。因此，这种LV可能对恒河猴等大型动物模型的长期安全性研究非常有用。
