Incoming human papillomavirus type 16 genome resides in a vesicular compartment throughout mitosis

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 113; no. 22; pp. 6289 - 6294
• Main Authors: DiGiuseppe, Stephen, Luszczek, Wioleta, Keiffer, Timothy R., Bienkowska-Haba, Malgorzata, Guion, Lucile G. M., Sapp, Martin J.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 31.05.2016
• Subjects: Biological Sciences; Cell Nucleus - metabolism; Cell Nucleus - virology; Cells; Chromosomes; Cytoplasmic Vesicles - metabolism; Cytoplasmic Vesicles - virology; Endosomes - metabolism; Endosomes - virology; Genome, Viral; Genomes; HeLa Cells; Human papillomavirus; Human papillomavirus 16; Human papillomavirus 16 - physiology; Humans; Membranes; Mitosis - physiology; Papillomavirus Infections - genetics; Papillomavirus Infections - metabolism; Papillomavirus Infections - virology; Protein Transport; Proteins; trans-Golgi Network - metabolism; trans-Golgi Network - virology; Virion; Virus Internalization; HPV entry; nuclear vesicle; mitosis; digitonin; vesicular transport
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1600638113

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.