title: Cleavage of the HPV16 Minor Capsid Protein L2 during Virion Morphogenesis Ablates the Requirement for Cellular Furin during De Novo Infection.
abstract: Infections by high-risk human papillomaviruses (HPV) are the causative agents for the development of cervical cancer. As with other non-enveloped viruses, HPVs are taken up by the cell through endocytosis following primary attachment to the host cell. Through studies using recombinant pseudovirus particles (PsV), many host cellular proteins have been implicated in the process. The proprotein convertase furin has been demonstrated to cleave the minor capsid protein, L2, post-attachment to host cells and is required for infectious entry by HPV16 PsV. In contrast, using biochemical inhibition by a furin inhibitor and furin-negative cells, we show that tissue-derived HPV16 native virus (NV) initiates infection independent of cellular furin. We show that HPV16 L2 is cleaved during virion morphogenesis in differentiated tissue. In addition, HPV45 is also not dependent on cellular furin, but two other alpha papillomaviruses, HPV18 and HPV31, are dependent on the activity of cellular furin for infection.
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. lcruz@hmc.psu.edu.
authors.forename: Linda
authors.initials: L
authors.lastname: Cruz
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. jhopkins@hmc.psu.edu.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Biryukov
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. conwa2m@cmich.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Conway
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA. cmm10@psu.edu.
authors.forename: Craig
authors.initials: C
authors.lastname: Meyers
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000378:metabolism*; D002460:Cell Line; D045683:Furin / Q000378:metabolism*; D052162:Human papillomavirus 16 / Q000254:growth & development* / Q000502:physiology; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D036022:Capsid Proteins; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D045683:Furin
keywords: HPV16; J0101; PACS; furin; human papillomavirus (HPV)