title: Roles for human papillomavirus type 16 l1 cysteine residues 161, 229, and 379 in genome encapsidation and capsid stability.
abstract: Human papillomavirus (HPV) capsids are formed through a network of inter- and intra-pentameric hydrophobic interactions and disulfide bonds. 72 pentamers of the major capsid protein, L1, and an unknown amount of the minor capsid protein, L2, form the structure of the capsid. There are 12 conserved L1 cysteine residues in HPV16. While C175, C185, and C428 have been implicated in the formation of a critical inter-pentameric disulfide bond, no structural or functional roles have been firmly attributed to any of the other conserved cysteine residues. Here, we show that substitution of cysteine residues C161, C229, and C379 for serine hinders the accumulation of endonuclease-resistant genomes as virions mature within stratifying and differentiating human epithelial tissue. C229S mutant virions form, but are non-infectious. These studies add detail to the differentiation-dependent assembly and maturation that occur during the HPV16 life cycle in human tissue.
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, United States of America.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Ryndock
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, United States of America.
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, Pennsylvania, United States of America.
authors.forename: Samina
authors.initials: S
authors.lastname: Alam
authors.affiliation: Health Care Biotechnology Department, Atta-ur-Rahman School of Applied Biosciences, National University of Science and Technology, Islamabad, Pakistan.
authors.forename: Sana
authors.initials: S
authors.lastname: Gul
authors.affiliation: Health Care Biotechnology Department, Atta-ur-Rahman School of Applied Biosciences, National University of Science and Technology, Islamabad, Pakistan.
authors.forename: Sheeba
authors.initials: S
authors.lastname: Murad
authors.affiliation: Department of Pathology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, United States of America.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Christensen
authors.affiliation: Department of Microbiology and Immunology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, United States of America.
authors.forename: Craig
authors.initials: C
authors.lastname: Meyers
mesh_terms: D002213:Capsid; D003545:Cysteine / Q000235:genetics*; D016679:Genome, Viral; D042822:Genomic Instability; D027383:Papillomaviridae / Q000235:genetics*; D014771:Virion
chemical_list: D003545:Cysteine