Molecular and macromolecular alterations of recombinant adenoviral vectors do not resolve changes in hepatic drug metabolism during infection.
In this report we test the hypothesis that long-term virus-induced alterations in CYP occur from changes initiated by the virus that may not be related to the immune response. Enzyme activity, protein expression and mRNA of CYP3A2, a correlate of human CYP3A4, and CYP2C11, responsive to inflammatory mediators, were assessed 0.25, 1, 4, and 14 days after administration of several different recombinant adenoviruses at a dose of 5.7 x 1012 virus particles (vp)/kg to male Sprague Dawley rats. Wild type adenovirus, containing all viral genes, suppressed CYP3A2 and 2C11 activity by 37% and 39%, respectively within six hours. Levels fell to 67% (CYP3A2) and 79% (CYP2C11) of control by 14 days (p
Adenoviridae, Adenoviridae Infections, Alanine Transaminase, Animals, Aryl Hydrocarbon Hydroxylases, Cell Line, Cells, Cultured, Cytochrome P-450 CYP3A, Cytochrome P450 Family 2, Gene Expression, Genetic Vectors, Hepatocytes, Humans, Liver, Male, Membrane Proteins, Rats, Rats, Sprague-Dawley, Steroid 16-alpha-Hydroxylase