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

Area of Science:

• Virology
• Infectious Diseases
• Molecular Biology

Background:

• Understanding papillomavirus (PV) infection mechanisms is crucial for developing antiviral strategies.
• Murine PV1 (MusPV1) is a newly described virus offering a model to compare with human PVs.
• Human PV16 (HPV16) serves as a benchmark for PV infection dynamics.

Purpose of the Study:

• To compare the infection mechanisms of murine MusPV1 with human HPV16.
• To investigate MusPV1 pseudovirion binding and infection in a murine cervicovaginal challenge model.
• To elucidate the role of host attachment factors in MusPV1 initial interactions.

Main Methods:

• Utilized a murine cervicovaginal challenge model to study MusPV1 infection.
• Examined pseudovirion binding to basement membrane (BM) and its dependence on heparan sulfate proteoglycans (HSPG).
• Assessed the impact of L2 antibodies, VLP antibodies, and furin inhibition on MusPV1 localization and infection.

Main Results:

• MusPV1 bound to BM independently of HSPG, unlike HPV16.
• Subsequent HSPG interactions were critical for MusPV1 infection.
• L2 antibodies, VLP antibodies, and furin inhibition did not cause MusPV1 dissociation from BM, contrasting with HPV16 findings.

Conclusions:

• Phylogenetically distant PV types exhibit distinct initial interactions with host attachment factors.
• Both MusPV1 and HPV16 initiate their lifecycle on the acellular basement membrane.
• Despite differing entry mechanisms, MusPV1 and HPV16 show similar intracellular trafficking and susceptibility to biochemical inhibition.