The Kirby Institute, University of New South Wales (UNSW), Sydney NSW 2052, Australia.
Viruses. 2018 Feb 5;10(2):63. doi: 10.3390/v10020063.
While significant progress has been made in terms of human immunodeficiency virus (HIV) therapy, treatment does not represent a cure and remains inaccessible to many people living with HIV. Continued mechanistic research into the viral life cycle and its intersection with many aspects of cellular biology are not only fundamental in the continued fight against HIV, but also provide many key observations of the workings of our immune system. Decades of HIV research have testified to the integral role of the actin cytoskeleton in both establishing and spreading the infection. Here, we review how the virus uses different strategies to manipulate cellular actin networks and increase the efficiency of various stages of its life cycle. While some HIV proteins seem able to bind to actin filaments directly, subversion of the cytoskeleton occurs indirectly by exploiting the power of actin regulatory proteins, which are corrupted at multiple levels. Furthermore, this manipulation is not restricted to a discrete class of proteins, but rather extends throughout all layers of the cytoskeleton. We discuss prominent examples of actin regulators that are exploited, neutralized or hijacked by the virus, and address how their coordinated deregulation can lead to changes in cellular behavior that promote viral spreading.
尽管在人类免疫缺陷病毒 (HIV) 治疗方面取得了重大进展，但治疗并不代表治愈，而且许多 HIV 感染者仍然无法获得治疗。对病毒生命周期及其与细胞生物学多个方面的交叉进行持续的机制研究，不仅对继续抗击 HIV 至关重要，而且还为我们免疫系统的工作提供了许多关键观察结果。几十年来的 HIV 研究证明了肌动蛋白细胞骨架在建立和传播感染方面的重要作用。在这里，我们回顾了病毒如何利用不同的策略来操纵细胞肌动蛋白网络并提高其生命周期各个阶段的效率。虽然一些 HIV 蛋白似乎能够直接结合肌动蛋白丝，但细胞骨架的颠覆是通过利用肌动蛋白调节蛋白的力量间接发生的，这些蛋白在多个层面上被破坏。此外，这种操纵不仅限于一类特定的蛋白质，而是扩展到细胞骨架的所有层。我们讨论了被病毒利用、中和或劫持的突出的肌动蛋白调节因子的例子，并探讨了它们的协调失调如何导致促进病毒传播的细胞行为变化。
