Vascular endothelial growth factor-A promotes Vaccinia virus entry into host cells via activation of the Akt pathway.

Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London. Charterhouse Square, London EC1M 6BQ. United Kingdom.
Journal of Virology (Impact Factor: 4.65). 12/2012; 87(5). DOI: 10.1128/JVI.00854-12
Source: PubMed

ABSTRACT Vaccinia virus (VV) is an enveloped DNA virus from the poxvirus family and has played a crucial role in the eradication of smallpox. It continues to be used in immunotherapy for prevention of infectious diseases and treatment of cancer. However, the mechanisms of poxvirus entry, the host factors that affect viral virulence and the reasons for its natural tropism for tumor cells are incompletely understood. By studying the effect of hypoxia on VV infection we found that vascular endothelial growth factor-A (VEGF) augments oncolytic VV cytotoxicity. VEGF derived from tumor cells acts to increase VV internalization resulting in increased replication and cytotoxicity in an AKT-dependent manner in both tumor cells and normal respiratory epithelial cells. Overexpression of VEGF also enhances VV infection within tumor tissue in vivo after systemic delivery. These results highlight the importance of VEGF expression in VV infection and have potential implications for the design of new strategies to prevent poxvirus infection and the development of future generations of oncolytic VV in combination with conventional or biological therapies.

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Available from: James R Tysome, Jun 18, 2014
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