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Journal of Virology, June 2006, p. 5655-5659, Vol. 80, No. 11
0022-538X/06/$08.00+0     doi:10.1128/JVI.00166-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Rapid Upregulation of Interferon-Regulated and Chemokine mRNAs upon Injection of 10⁸ International Units, but Not Lower Doses, of Adenoviral Vectors into the Brain

Board of Governors’ Gene Therapeutics Research Institute, Cedar-Sinai Medical Center, and Departments of Medical and Molecular Pharmacology and Medicine, David Geffen School of Medicine, University of California, Los Angeles, California,¹ Scripps Research Institute, La Jolla, California,² University of Sydney, Sydney, Australia³

Received 24 January 2006/ Accepted 6 March 2006

The innate immune response, characterized by the rapid induction of proinflammatory genes, plays an important role in immune responses to viral vectors utilized in gene therapy. We demonstrate that several innate proinflammatory mRNAs, i.e., those coding for the interferon (IFN)-regulated proteins interferon regulatory factor 1, 2',5'-oligoadenylate synthetase, and double-stranded-RNA-dependent protein kinase as well as those coding for the chemokines RANTES, IFN--inducible protein 10, and monocyte chemoattractant protein 1, were all increased in a statistically significant manner in response to 1 x 10⁸ IU, but not lower doses, of a first-generation adenovirus injected into the naïve brain. This indicates the presence of a threshold dosage of adenovirus needed to elicit an acute innate inflammatory response.

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