Jayappa Kallesh Danappa, Ao Zhujun, Yao Xiaojian
Laboratory of Molecular Human Retrovirology, Department of Medical Microbiology, Faculty of Medicine, University of Manitoba Winnipeg, MB, Canada.
Int J Biochem Mol Biol. 2012;3(1):70-85. Epub 2012 Feb 25.
The human immunodeficiency virus 1 (HIV-1) synthesizes its genomic DNA in cytoplasm as soon as it enters the cell. The newly synthesized DNA remains associated with viral/cellular proteins as a high molecular weight pre-integration complex (PIC), which precludes passive diffusion across intact nuclear membrane. However, HIV-1 successfully overcomes nuclear membrane barrier by actively delivering its DNA into nucleus with the help of host nuclear import machinery. Such ability allows HIV-1 to productively infect non-dividing cells as well as dividing cells at interphase. Further, HIV-1 nuclear import is also found important for the proper integration of viral DNA. Thus, nuclear import plays a crucial role in establishment of infection and disease progression. While several viral components, including matrix, viral protein R, integrase, capsid, and central DNA flap are implicated in HIV-1 nuclear import, their molecular mechanism remains poorly understood. In this review, we will elaborate the role of individual viral factors and some of current insights on their molecular mechanism(s) associated with HIV-1 nuclear import. In addition, we will discuss the importance of nuclear import for subsequent step of viral DNA integration. Hereby we aim to further our understanding on molecular mechanism of HIV-1 nuclear import and its potential usefulness for anti-HIV-1 strategies.
人类免疫缺陷病毒1型(HIV-1)一旦进入细胞,就会在细胞质中合成其基因组DNA。新合成的DNA作为高分子量的预整合复合物(PIC)与病毒/细胞蛋白保持关联,这阻止了其通过完整核膜的被动扩散。然而,HIV-1借助宿主核输入机制将其DNA主动输送到细胞核中,从而成功克服了核膜屏障。这种能力使HIV-1能够有效感染非分裂细胞以及处于间期的分裂细胞。此外,还发现HIV-1的核输入对于病毒DNA的正确整合也很重要。因此,核输入在感染的建立和疾病进展中起着关键作用。虽然包括基质、病毒蛋白R、整合酶、衣壳和中央DNA侧翼在内的几种病毒成分与HIV-1的核输入有关,但其分子机制仍知之甚少。在这篇综述中,我们将阐述各个病毒因子的作用以及目前对其与HIV-1核输入相关分子机制的一些见解。此外,我们还将讨论核输入对病毒DNA整合后续步骤的重要性。在此,我们旨在进一步了解HIV-1核输入的分子机制及其在抗HIV-1策略中的潜在用途。