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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Laimins, Laimonis A. Moody, Cary A. Fradet-turcotte, Amelie Archambault, Jacques |
| Description | Author Affiliation: Moody CA ( Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.); |
| Abstract | The life cycle of human papillomaviruses (HPVs) is linked to epithelial differentiation, with late viral events restricted to the uppermost stratified layers. Our studies indicated that HPV activates capases-3, -7, and -9 upon differentiation, whereas minimal activation was observed in differentiating normal keratinocytes. Activation occurred in the absence of significant levels of apoptosis, suggesting a potential role for caspases in the viral life cycle. In support of this, the addition of caspase inhibitors significantly impaired differentiation-dependent viral genome amplification. A conserved caspase cleavage motif was identified in the replication protein E1 ((46)DxxD(49)) that was targeted in vitro by both recombinant caspase-3 and caspase-7. Mutation of this site inhibited amplification of viral genomes, indicating that caspase cleavage is necessary for the productive viral life cycle. Our study demonstrates that HPV activates caspases upon differentiation to facilitate productive viral replication and represents a way by which HPV controls viral gene function in differentiating cells. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 49 |
| Volume Number | 104 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2007-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Alphapapillomavirus Physiology Apoptosis Caspases Metabolism Keratinocytes Virology Viral Proteins Virus Replication Genetics Cell Differentiation Cell Line Genome, Viral Cytology Enzymology Oncogene Proteins, Viral Substrate Specificity Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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