Molecular and macromolecular alterations of recombinant adenoviral vectors do not resolve changes in hepatic drug metabolism during infection.
Virol J. 2008; 5: 111.
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, Gene Expression, Genetic Vectors, Hepatocytes, Humans, Liver, Male, Membrane Proteins, Rats, Rats, Sprague-Dawley, Steroid 16-alpha-Hydroxylase