Article

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: 4.44). 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 the 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-A) 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.

Full-text

Available from: James R Tysome, Jun 18, 2014