Use of an in vivo animal model for assessing the role of integrin α6β4 and Syndecan-1 in early steps in papillomavirus infection

Human papillomaviruses (HPV) are small DNA tumor viruses. HPV infection requires entry of virions into epithelial host cells that support the viral life cycle. Here, we used an in vivo mouse model, in which HPV pseudoviruses (PVs) are scored for their ability to transduce reporter genes, to test the role of various cellular proteins in entry. We initially investigated the role of integrin alpha(6)beta(4) in mediating early steps of HPV infection. Deficiency of integrin alpha(6)beta(4) is modestly but significantly suppressed reporter-gene transduction by PVs in conditional integrin beta(4) knockout mice. We also investigated the role of syndecan 1, a heparin sulfate proteoglycan (HSPG) for its role in HPV infection. We did not see a significant reduction in reporter-gene transduction by PVs in syndecan-1 null mice. This indicates that this HSPG is not essential for early steps in HPV infection, but does not discount a need of other HSPGs in mediating HPV infection. (C) 2012 Elsevier Inc. All rights reserved.