Viral hijacking of host molecular motors to promote nuclear entry

During entry, most DNA viruses must navigate the crowded cellular environment to reach the nucleus where transcription and replication of the viral genome occur. How polyomavirus (PyV), a small, DNA tumor virus, accomplishes this essential step in infection is unclear. In mammalian cells, intracellular transport is facilitated largely by two host motors, kinesin and cytoplasmic dynein, which move cargo along microtubules towards the periphery and center of the cell, respectively. We reported that dynein motor activity is required for PyV disassembly and nuclear arrival, but the exact mechanisms by which it promotes this process were unknown. Processive dynein activity requires a three-protein complex composed of the dynein motor, dynactin activator and an adaptor that confers cargo specificity. Unexpectedly, our most recent data revealed that the BICD2 adaptor is sufficient to disassemble the virus independent of the other components within the complex revealing cargo remodeling as a novel function of dynein adaptors. As BICD2 associates with both dynein and kinesin and is involved in cargo transport to the nuclear membrane, we are now investigating the role of these factors in the subsequent nuclear arrival and import of PyV.

Host: Matt Chapman