Rapid upregulation of interferon-regulated and chemokine mRNAs upon injection of 108 International Units, but not lower doses, of adenoviral vectors into the brain

Jeffrey M. Zirger, Carlos Barcia, Chunyan Liu, Mariana Puntel, Ngan Mitchell, Iain Campbell, Maria Castro, Pedro R. Lowenstein*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

17 Citations (Scopus)

Abstract

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-γ-inducible protein 10, and monocyte chemoattractant protein 1, were all increased in a statistically significant manner in response to 1 × 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.

Original languageEnglish
Pages (from-to)5655-5659
Number of pages5
JournalJournal of Virology
Volume80
Issue number11
DOIs
Publication statusPublished - Jun 2006

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