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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Mazzon, Michela Ferguson, Brian J. Peters, Nicholas E. Krysztofinska, Ewelina M. Ember, Stuart W. J. Loenarz, Christoph Smith, Geoffrey L. |
| Description | Author Affiliation: Mazzon M ( Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom.); |
| Abstract | Viruses have evolved sophisticated strategies to exploit host cell function for their benefit. Here we show that under physiologically normal oxygen levels (normoxia) vaccinia virus (VACV) infection leads to a rapid stabilization of hypoxia-inducible factor (HIF)-1 , its translocation into the nucleus and the activation of HIF-responsive genes, such as vascular endothelial growth factor (VEGF), glucose transporter-1, and pyruvate dehydrogenase kinase-1. HIF-1 stabilization is mediated by VACV protein C16 that binds the human oxygen sensing enzyme prolyl-hydroxylase domain containing protein (PHD)2 and thereby inhibits PHD2-dependent hydroxylation of HIF-1 . The binding between C16 and PHD2 is direct and specific, and ectopic expression of C16 alone induces transcription of HIF-1 responsive genes. Conversely, a VACV strain lacking the gene for C16, C16L, is unable to induce HIF-1 stabilization. Interestingly, the N-terminal region of C16 is predicted to have a PHD2-like structural fold but lacks the catalytic active site residues of PHDs. The induction of a hypoxic response by VACV is reminiscent of the biochemical consequences of solid tumor formation, and illustrates a poxvirus strategy for manipulation of cellular gene expression and biochemistry. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 30 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cell Hypoxia Physiology Vaccinia Virus Amino Acid Sequence HEK293 Cells Hydroxylation Hypoxia-Inducible Factor 1, Alpha Subunit Metabolism Hypoxia-Inducible Factor-Proline Dioxygenases Molecular Sequence Data Procollagen-Proline Dioxygenase Sequence Homology, Amino Acid Viral Proteins Chemistry Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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