Altered amino acid metabolic patterns in the plasma of rat models with adenovirus infection.

Abstract

The presence of replication-competent adenovirus (RCA) subpopulations in adenoviral vector products raises a variety of safety issues for development of therapies based on gene therapy. To analyze the differing effects of adenoviral vector and RCA in vivo, we examined alterations in amino acids (AAs) using rat plasma following injection of β-galactosidase expressing recombinant adenovirus (designated rAdLacZ) or RCA. Plasma AAs were examined by gas chromatography-mass spectrometry. A total of 16 AAs were positively measured. In the rAdLacZ group compared to the control group, the level of aspartic acid was significantly increased (Student's t-test), while the level of glutamic acid was significantly reduced. Additionally, in the RCA group compared to the control group, the level of four AAs, valine, leucine, and isoleucine as branched-chain amino acids, and proline were significantly increased, whereas the levels of three AAs, glycine, threonine, and glutamic acid were significantly reduced. Altered plasma free AA metabolic patterns in rAdLacZ and RCA groups, compared with the control group, may explain the disturbance of AA metabolism related to viral infection.