Journal
VIROLOGY
Volume 475, Issue -, Pages 1-14Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2014.10.035
Keywords
Oncolytic virus; VSV; Antiviral; Brain; Interferon; Ribavirin; AAV
Categories
Funding
- National Institutes of Health [CA124737, CA161048, CA175577, K08CA169005]
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Vesicular stomatitis virus (VSV) shows promise as a vaccine-vector and oncolytic virus. However, reports of neurotoxicity of VSV remain a concern. We compared 12 antiviral compounds to control infection of VSV-CT9-M51 and VSV-rp30 using murine and human brain cultures, and in vivo mouse models. Inhibition of replication, cytotoxicity and infectivity was strongest with ribavirin and IFN-alpha and to some extent with mycophenolic acid, chloroquine, and adenine 9-beta-D-arabinofuranoside. To generate continuous IFN exposure, we made an adeno-associated virus vector expressing murine IFN; AAV-mIFN-beta protected mouse brain cells from VSV, as did a combination of IFN, ribavirin and chloroquine. Intracranial AAV-mIFN-beta protected the brain against VSV-CT9-M51. In SCID mice bearing human glioblastoma, AAV-mIFN-beta moderately enhanced survival. VSV-CT9-M51 doubled median survival when administered after AAV-mIFN-beta; some surviving mice showed complete tumor destruction. Together, these data suggest that AAV-IFN or IFN with ribavirin and chloroquine provide an optimal anti-virus combination against VSV in the brain. (C) 2014 Elsevier Inc. All rights reserved.
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