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Virology. 2015 Jan 15;475:1-14. doi: 10.1016/j.virol.2014.10.035. Epub 2014 Nov 21.

Attenuation of vesicular stomatitis virus infection of brain using antiviral drugs and an adeno-associated virus-interferon vector.

Author information

1
Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, United States.
2
Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520, United States. Electronic address: anthony.vandenpol@yale.edu.

Abstract

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-α and to some extent with mycophenolic acid, chloroquine, and adenine 9-β-d-arabinofuranoside. To generate continuous IFN exposure, we made an adeno-associated virus vector expressing murine IFN; AAV-mIFN-β protected mouse brain cells from VSV, as did a combination of IFN, ribavirin and chloroquine. Intracranial AAV-mIFN-β protected the brain against VSV-CT9-M51. In SCID mice bearing human glioblastoma, AAV-mIFN-β moderately enhanced survival. VSV-CT9-M51 doubled median survival when administered after AAV-mIFN-β; 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.

KEYWORDS:

AAV; Antiviral; Brain; Interferon; Oncolytic virus; Ribavirin; VSV

PMID:
25462341
PMCID:
PMC4326005
DOI:
10.1016/j.virol.2014.10.035
[Indexed for MEDLINE]
Free PMC Article

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