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Journal of Virology, May 2000, p. 4816-4823, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Liver-Specific Alpha 2 Interferon Gene Expression Results in Protection from Induced Hepatitis

Luigi Aurisicchio, Paola Delmastro, Valentina Salucci, Odalys Gonzalez Paz, Patrizia Rovere, Gennaro Ciliberto, Nicola La Monica, and Fabio Palombo*

IRBM P. Angeletti, Rome, Italy

Received 22 September 1999/Accepted 4 February 2000

The current therapy for hepatitis B and C is based on systemic administration of recombinant human alpha interferon (r-hIFN-alpha ). However, systemic delivery of r-hIFN-alpha is associated with severe side effects, but more importantly, it is effective in only a small percentage of patients. In an effort to maximize IFN-alpha antiviral efficacy, we have explored the therapeutic potential of murine IFN-alpha 2 (mIFNalpha 2) selectively expressed in the liver. To this end, we have developed a helper-dependent adenovirus vector (HD) containing the mIFN-alpha 2 gene under the control of the liver-specific transthyretin promoter (HD-IFN). Comparison with a first-generation adenovirus carrying the same mIFN-alpha 2 expression cassette indicates that at certain HD-IFN doses, induction of antiviral genes can be achieved in the absence of detectable circulating mIFN-alpha 2. Challenge of injected mice with mouse hepatitis virus type 3 showed that HD-IFN provides high liver protection. Moreover, liver protection was also observed in acute nonviral liver inflammation hepatitis induced by concanavalin A at 1 month postinfection. These results hold promise for the development of a gene therapy treatment for chronic viral hepatitis based on liver-restricted expression of IFN-alpha 2.

* Corresponding author. Mailing address: IRBM P. Angeletti, Via Pontina Km 30,600, 00040 Pomezia (Rome), Italy. Phone: 39-06-91093-234. Fax: 39-06-91093-225. E-mail: palombo{at}irbm.it.

Journal of Virology, May 2000, p. 4816-4823, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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