Virus activated filopodia promote human papillomavirus type 31 uptake from the extracellular matrix.

Human papillomaviruses (HPVs), etiological agents of epithelial tumors and cancers, initiate infection of basal human keratinocytes (HKs) facilitated by wounding. Virions bind to HKs and their secreted extracellular matrix (ECM), but molecular roles for wounding or ECM binding during infection are unclear. Herein we demonstrate that HPV31 activates signals promoting cytoskeletal rearrangements and virion transport required for internalization and infection. Activation of tyrosine and PI3 kinases precedes induction of filopodia whereon virions are transported toward the cell body. Coupled with the loss of ECM-bound virions this supports a model whereby virus activated filopodial transport contributes to an increased and protracted virion uptake into susceptible cells.