HPV16 entry requires dynein for minus-end transport and utilizes kinesin Kif11 for plus-end transport along microtubules during mitosis

Abstract

Human papillomaviruses (HPV) utilize a unique vesicular structure to shield their genomes from detection during trafficking from the trans-Golgi network (TGN) to the nucleus during mitosis. The exact cellular factors responsible for trafficking these HPV genome containing vesicles along mitotic microtubules via the L2 minor protein remain unknown. We show via high-resolution microscopy that pharmacological inhibition of dynein and the kinesin Kif11 significantly decreases HPV pseudogenome accumulation on mitotic chromatin. Several kinesins were detected in proximity to incoming HPV pseudogenomes. Finally, using a novel knocksideways approach, we show reduced HPV pseudogenome accumulation on mitotic chromatin upon Kif11 relocalization to the mitochondria. Herein, our data suggest HPV utilizes minus- and plus-end mediated trafficking along mitotic microtubules to complete its genome trafficking to the nucleus.