The HPV16 and MusPV1 papillomaviruses initially interact with distinct host components on the basement membrane.

To understand and compare the mechanisms of murine and human PV infection, we examined pseudovirion binding and infection of the newly described MusPV1 using the murine cervicovaginal challenge model. These analyses revealed primary tissue interactions distinct from those previously described for HPV16. Unlike HPV16, MusPV1 bound basement membrane (BM) in an HSPG-independent manner. Nevertheless, subsequent HSPG interactions were critical. L2 antibodies or low doses of VLP antibodies, sufficient to prevent infection, did not lead to disassociation of the MusPV1 pseudovirions from the BM, in contrast to previous findings with HPV16. Similarly, furin inhibition did not lead to loss of MusPV1 from the BM. Therefore, phylogenetically distant PV types differ in their initial interactions with host attachment factors, but initiate their lifecycle on the acellular BM. Despite these differences, these distantly related PV types displayed similar intracellular trafficking patterns and susceptibilities to biochemical inhibition of infection.