Liver-Specific Alpha 2 Interferon Gene Expression Results in Protection from Induced Hepatitis
| Autor: | Fabio Palombo, Paola Delmastro, Luigi Aurisicchio, Gennaro Ciliberto, Odalys Gonzalez Paz, Valentina Salucci, Nicola La Monica, Patrizia Rovere |
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| Rok vydání: | 2000 |
| Předmět: |
Genetic Vectors
Immunology Gene Expression Alpha interferon Biology medicine.disease_cause Microbiology Adenoviridae Viral vector Mice Mouse hepatitis virus Interferon Virology Concanavalin A medicine Animals Humans Hepatitis Murine hepatitis virus Interferon-alpha Genetic Therapy Gene Therapy Hepatitis B medicine.disease biology.organism_classification Mice Inbred C57BL Liver Hepatitis Viral Animal Insect Science Female Chemical and Drug Induced Liver Injury Viral hepatitis Helper Viruses medicine.drug |
| Zdroj: | Journal of Virology. 74:4816-4823 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.74.10.4816-4823.2000 |
| Popis: | 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-alpha2 (mIFNalpha2) selectively expressed in the liver. To this end, we have developed a helper-dependent adenovirus vector (HD) containing the mIFN-alpha2 gene under the control of the liver-specific transthyretin promoter (HD-IFN). Comparison with a first-generation adenovirus carrying the same mIFN-alpha2 expression cassette indicates that at certain HD-IFN doses, induction of antiviral genes can be achieved in the absence of detectable circulating mIFN-alpha2. 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-alpha2. |
| Databáze: | OpenAIRE |
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