title: Cell surface-binding motifs of L2 that facilitate papillomavirus infection.
abstract: Human papillomavirus type 16 (HPV16) is the primary etiologic agent of cervical carcinoma, whereas bovine papillomavirus type 1 (BPV1) causes benign fibropapillomas. However, the capsid proteins, L1 and L2, of these divergent papillomaviruses exhibit functional conservation. A peptide comprising residues 1 to 88 of BPV1 L2 binds to a variety of cell lines, but not to the monocyte-derived cell line D32, and blocks BPV1 infection of mouse C127 cells. Residues 13 to 31 of HPV16 L2 and BPV1 L2 residues 1 to 88 compete for binding to the cell surface, and their binding, unlike that of HPV16 L1/L2 virus-like particles, is unaffected by heparinase or trypsin pretreatment of HeLa cells. A fusion of HPV16 L2 peptide 13-31 and GFP binds (K(d), approximately 1 nM) to approximately 45,000 receptors per HeLa cell. Furthermore, mutation of L2 residues 18 and 19 or 21 and 22 significantly reduces both the ability of the HPV16 L2 13-31-GFP fusion protein to bind to SiHa cells and the infectivity of HPV16 pseudovirions. Antibody to BPV1 L2 peptides comprising residues 115 to 135 binds to intact BPV1 virions, but fails to neutralize at a 1:10 dilution. However, deletion of residues 91 to 129 from L2 abolishes the infectivity of BPV1, but not their binding to the cell surface. In summary, L2 residues 91 to 129 contain epitopes displayed on the virion surface and are required for infection, but not virion binding to the cell surface. Upon the binding of papillomavirus to the cell surface, residues 13 to 31 of L2 interact with a widely expressed, trypsin- and heparinase-resistant cell surface molecule and facilitate infection.
authors.affiliation: Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Rongcun
authors.initials: R
authors.lastname: Yang
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Day
authors.forename: William H
authors.initials: WH
authors.lastname: Yutzy
authors.forename: Ken-Yu
authors.initials: KY
authors.lastname: Lin
authors.forename: Chien-Fu
authors.initials: CF
authors.lastname: Hung
authors.forename: Richard B S
authors.initials: RB
authors.lastname: Roden
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D052688:Bovine papillomavirus 1 / Q000378:metabolism / Q000472:pathogenicity*; D002213:Capsid / Q000737:chemistry* / Q000378:metabolism; D036022:Capsid Proteins; D002417:Cattle; D002460:Cell Line; D019763:Heparin Lyase / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009856:Oncogene Proteins, Viral / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D027383:Papillomaviridae / Q000378:metabolism / Q000472:pathogenicity*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism*; D014357:Trypsin / Q000378:metabolism; D014771:Virion / Q000737:chemistry / Q000378:metabolism / Q000472:pathogenicity
chemical_list: D036022:Capsid Proteins; C085218:L2 protein, Bovine papillomavirus; C063316:L2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D010455:Peptides; D011991:Receptors, Virus; D014357:Trypsin; D019763:Heparin Lyase