Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 22, Pages 6289-6294Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1600638113
Keywords
HPV entry; vesicular transport; mitosis; digitonin; nuclear vesicle
Categories
Funding
- National Institutes of Allergy and Infectious Diseases [R01 AI081809, R01 DE0166908S1]
- National Institutes of Dental and Cranofacial Research
- National Institute of General Medical Sciences [P20GM103433]
- Feist Weiller Cancer Center
- Carroll Feist predoctoral fellowship
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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.
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