HIV-1 binds dynein directly to hijack microtubule transport machinery

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.