Role of Kinesins in Cytoplasmic Exploration by Adenovirus

A number of viruses exhibit microtubule-based bidirectional transport following cell entry. This behavior raises three questions: First, what mediates their transport along microtubules? Second, how do viruses recruit the motor proteins? Finally, how do they go to the right place by bidirectional transport in a variety of cell types with different microtubule organizations? We studied these questions with Adenovirus 5 (Ad5), a virus with well characterized, dynein-mediated minus transport mechanism. One form of plus end directed motor, Kif5C, has been reported to disrupt Ad5 capsids at the Nuclear Pore Complexes(NPC), but the mechanisms and roles of microtubule plus end-directed Ad5 transport prior to this stage are largely unknown. Here we performed a RNAi screen of 38 microtuble plus end-directed kinesins, which implicated Kif5B (kinesin-1 family) in plus-end directed Ad5 transport, along with several other forms of kinesin. Kif5B knockdown caused an accumulation of Ad5 particles near the centrosomes in human pulmonary epithelial A549 cells. This effect was strongly enhanced by blocking Ad5 nuclear pore targeting with Leptomycin B and supports a role for Kif5B in Ad5 transport pr