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

ZIRGER; BARCIA; LIU; PUNTEL; MITCHELL; CAMPBEL; CASTRO; LOWENSTEIN

JOURNAL OF VIROLOGY

AMER SOC MICROBIOLOGY

Año: 2006 p. 5655 - 5659

0022-538X

The innate immune response, characterized by the rapid induction of proinflammatory genes, plays animportant role in immune responses to viral vectors utilized in gene therapy. We demonstrate that severalinnate proinflammatory mRNAs, i.e., those coding for the interferon (IFN)-regulated proteins interferonregulatory factor 1, 2,5-oligoadenylate synthetase, and double-stranded-RNA-dependent protein kinase aswell as those coding for the chemokines RANTES, IFN--inducible protein 10, and monocyte chemoattractantprotein 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 naı¨ve brain. This indicates the presence of a threshold dosageof adenovirus needed to elicit an acute innate inflammatory response.