HIV-1 Engages a Dynein-Dynactin-BICD2 Complex for Infection and Transport to the Nucleus
Carnes, Stephanie Kaye
HIV-1 infection depends on efficient intracytoplasmic transport of the incoming viral core to the target cell nucleus. Evidence suggests that this movement is facilitated by the microtubule motor dynein, a large multi-protein complex that interacts with dynactin and cargo-specific adaptor proteins for retrograde movement via microtubules. Dynein adaptor proteins are necessary for activating dynein movement and for linking specific cargoes to dynein. I hypothesized that HIV-1 engages the dynein motor complex via an adaptor for intracellular transport. Here, I show that siRNA depletion of the dynein heavy chain, components of the dynactin complex, and the dynein adaptor BICD2, reduced cell permissiveness to HIV-1 infection. Cell depletion of dynein heavy chain and BICD2 resulted in impaired HIV-1 DNA accumulation in the nucleus and decreased retrograde movement of the virus. Biochemical studies revealed that dynein components and BICD2 associate with capsid-like assemblies of the HIV-1 CA protein in cell extracts and that purified recombinant BICD2 binds to CA assemblies in vitro. Association of dynein with CA assemblies was reduced upon immunodepletion of BICD2 from cell extracts. I conclude that BICD2 is a capsid-associated dynein adaptor utilized by HIV-1 for transport to the nucleus.