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PMID: 15383670 Published · ppublish English Journal Article

Establishment of papillomavirus infection is enhanced by promyelocytic leukemia protein (PML) expression.

Day PM, Baker CC, Lowy DR, Schiller JT

Abstract

Previous studies have suggested that most papillomaviruses enter the host cell via clathrin-dependent receptor-mediated endocytosis but have not addressed later steps in viral entry. To examine these events, we followed the localization of L2 and packaged DNA after entry of infectious virions or L1/L2 pseudovirions. Confocal microscopic analyses of HeLa cells showed a time-dependent uncoating of capsids in cytoplasmic vesicles and the accumulation of both L2 and viral DNA at distinct nuclear domains identified as nuclear domain 10 (ND10). Both L2 and the pseudogenome had a punctate distribution and localized to ND10 in promyelocytic leukemia protein (PML)-expressing cells, whereas L2 had a diffuse nuclear distribution in PML-/- cells. The number of pseudovirus-infected cells was an order of magnitude higher in the PML+ cells compared with the PML-/- cells, and viral genome transcription after infection with authentic bovine papillomavirus virions was similarly elevated in PML+ cells. The results identify a role for PML in the enhancement of viral infectivity in the early part of the life cycle. We propose a model in which L2 chaperones the viral genome to ND10 to efficiently initiate viral transcription.

MeSH Terms
Animals Bovine papillomavirus 1/growth & development,pathogenicity,physiology Capsid Proteins/genetics,metabolism Cattle Cell Nucleus/metabolism,virology DNA, Viral/genetics,metabolism Gene Expression HeLa Cells Humans Mice Microscopy, Confocal Neoplasm Proteins/biosynthesis,genetics,metabolism Nuclear Proteins/biosynthesis,genetics,metabolism Papillomavirus Infections/metabolism Promyelocytic Leukemia Protein Pseudogenes/physiology Recombinant Fusion Proteins/genetics,metabolism Transcription Factors/biosynthesis,genetics,metabolism Transduction, Genetic Tumor Suppressor Proteins Zinc Fingers
Chemicals
Capsid Proteins DNA, Viral L2 protein, Bovine papillomavirus Neoplasm Proteins Nuclear Proteins Pml protein, mouse Promyelocytic Leukemia Protein Recombinant Fusion Proteins Transcription Factors Tumor Suppressor Proteins PML protein, human
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Day Patricia M
Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. pmd@nih.gov
Baker Carl C
Lowy Douglas R
Schiller John T
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2004-09-28
Epub
2004-00-21
Pages
14252-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC521143
Subset
IM
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