Badieyan Somayesadat, Lichon Drew, Keceli Sevnur Komurlu, Andreas Michael P, Gillies John P, Peng Wang, Shi Jiong, DeSantis Morgan E, Aiken Christopher R, Böcking Till, Giessen Tobias W, Campbell Edward M, Cianfrocco Michael A
Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Chicago, IL, USA.
Sci Adv. 2025 Jun 20;11(25):eadn6796. doi: 10.1126/sciadv.adn6796. Epub 2025 Jun 18.
HIV-1 uses the microtubule cytoskeleton to reach the host cell nucleus during replication, yet the molecular basis for microtubule-dependent HIV-1 motility is poorly understood. Using in vitro reconstitution biochemistry and single-molecule imaging, we found that HIV-1 binds to the retrograde microtubule-associated motor, dynein, directly and not via a cargo adaptor, as has been previously suggested. The HIV-1 capsid lattice binds to accessory chains on dynein's tail domain. Further, we demonstrate that multiple dynein motors tethered to rigid cargoes, such as HIV-1 capsids, display reduced motility, distinct from the behavior of multiple motors on membranous cargoes. Our results provide an updated model of HIV-1 trafficking wherein HIV-1 binds to dynein directly to "hijack" the dynein transport machinery for microtubule motility.
HIV-1在复制过程中利用微管细胞骨架抵达宿主细胞核，但对于依赖微管的HIV-1运动的分子基础却知之甚少。通过体外重组生物化学和单分子成像技术，我们发现HIV-1直接与逆行微管相关的动力蛋白动力蛋白结合，而非如先前推测的那样通过货物衔接蛋白结合。HIV-1衣壳晶格与动力蛋白尾部结构域上的辅助链结合。此外，我们证明，拴系在诸如HIV-1衣壳等刚性货物上的多个动力蛋白马达显示出运动能力降低，这与膜性货物上多个马达的行为不同。我们的研究结果提供了一个更新的HIV-1运输模型，其中HIV-1直接与动力蛋白结合，以“劫持”动力蛋白运输机制进行微管运动。
