title: The nuclear retention signal of HPV16 L2 protein is essential for incoming viral genome to transverse the trans-Golgi network.
abstract: The Human papillomavirus (HPV) capsid is composed of the major and minor capsid proteins, L1 and L2, respectively. Infectious entry requires a complex series of conformational changes in both proteins that lead to uptake and allow uncoating to occur. During entry, the capsid is disassembled and host cyclophilins dissociate L1 protein from the L2/DNA complex. Herein, we describe a mutant HPV16 L2 protein (HPV16 L2-R302/5A) that traffics pseudogenome to the trans-Golgi network (TGN) but fails to egress. Our data provide further evidence that HPV16 traffics through the TGN and demonstrates that L2 is essential for TGN egress. Furthermore, we show that cyclophilin activity is required for the L2/DNA complex to be transported to the TGN which is accompanied by a reduced L1 protein levels.
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Feist-Weiller Cancer Center, LSU Health Shreveport, Shreveport, LA, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: DiGiuseppe
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Feist-Weiller Cancer Center, LSU Health Shreveport, Shreveport, LA, USA.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Bienkowska-Haba
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Feist-Weiller Cancer Center, LSU Health Shreveport, Shreveport, LA, USA.
authors.forename: Lydia
authors.initials: L
authors.lastname: Hilbig
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Feist-Weiller Cancer Center, LSU Health Shreveport, Shreveport, LA, USA. Electronic address: msapp1@lsuhsc.edu.
authors.forename: Martin
authors.initials: M
authors.lastname: Sapp
mesh_terms: D036022:Capsid Proteins / Q000737:chemistry / Q000378:metabolism*; D016679:Genome, Viral; D057809:HEK293 Cells; D006367:HeLa Cells; D052162:Human papillomavirus 16 / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D019913:Nuclear Localization Signals / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport; D053586:Virus Internalization; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: D036022:Capsid Proteins; C063316:L2 protein, Human papillomavirus type 16; D019913:Nuclear Localization Signals; D009856:Oncogene Proteins, Viral
keywords: Cyclophilin; Entry; HPV; L1; L2; Trans-Golgi network