title: Incoming human papillomavirus type 16 genome resides in a vesicular compartment throughout mitosis.
abstract: During the entry process, the human papillomavirus (HPV) capsid is trafficked to the trans-Golgi network (TGN), whereupon it enters the nucleus during mitosis. We previously demonstrated that the minor capsid protein L2 assumes a transmembranous conformation in the TGN. Here we provide evidence that the incoming viral genome dissociates from the TGN and associates with microtubules after the onset of mitosis. Deposition onto mitotic chromosomes is L2-mediated. Using differential staining of an incoming viral genome by small molecular dyes in selectively permeabilized cells, nuclease protection, and flotation assays, we found that HPV resides in a membrane-bound vesicle until mitosis is completed and the nuclear envelope has reformed. As a result, expression of the incoming viral genome is delayed. Taken together, these data provide evidence that HPV has evolved a unique strategy for delivering the viral genome to the nucleus of dividing cells. Furthermore, it is unlikely that nuclear vesicles are unique to HPV, and thus we may have uncovered a hitherto unrecognized cellular pathway that may be of interest for future cell biological studies.
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, LSU Health Shreveport, Shreveport, LA 71130.
authors.forename: Stephen
authors.initials: S
authors.lastname: DiGiuseppe
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, LSU Health Shreveport, Shreveport, LA 71130.
authors.forename: Wioleta
authors.initials: W
authors.lastname: Luszczek
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, LSU Health Shreveport, Shreveport, LA 71130.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Keiffer
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, LSU Health Shreveport, Shreveport, LA 71130.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Bienkowska-Haba
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, LSU Health Shreveport, Shreveport, LA 71130.
authors.forename: Lucile G M
authors.initials: LG
authors.lastname: Guion
authors.affiliation: Department of Microbiology and Immunology, Center for Molecular and Tumor Virology and Feist-Weiller Cancer Center, LSU Health Shreveport, Shreveport, LA 71130 msapp1@lsuhsc.edu.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Sapp
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism / Q000821:virology; D022162:Cytoplasmic Vesicles / Q000378:metabolism* / Q000821:virology; D011992:Endosomes / Q000378:metabolism / Q000821:virology; D016679:Genome, Viral; D006367:HeLa Cells; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D021381:Protein Transport; D014771:Virion; D053586:Virus Internalization; D021601:trans-Golgi Network / Q000378:metabolism / Q000821:virology
keywords: HPV entry; digitonin; mitosis; nuclear vesicle; vesicular transport