The 2-5A system and HIV infection

Abstract

2',5'-Oligoadenylates (2-5A) have an essential role in the establishment of the antiviral state of a cell exposed to virus infection. The key enzymes of the 2-5A system are the 2-5A forming 2',5'-oligoadenylate synthetase (2-5OAS), the activity of which depends on the presence of viral or cellular double-stranded RNA (dsRNA), and the 2-5A-activated ribonuclease (RNase L). Basic research in recent years has shown that the 2-5A system is a promising target for anti-HIV chemotherapy, particularly due to its interaction with double-stranded segments within HIV RNA. Two new strategies have been developed which yield a selective antiviral effect of 2-5A against HIV-1 infection: (1) development of 2-5A analogues displaying a dual mode of action (activation of RNase L and inhibition of HIV-1 RT) and (2) intracellular immunization of cells against HIV-1 infection by application of the HIV-1-LTR--2-5OAS hybrid gene. A further strategy is the inhibition of DNA topoisomerase I by longer 2-5A oligomers.