0000000000583252
AUTHOR
Wolfgang Pfleiderer
Cordycepin analogues of 2',5'-oligoadenylate inhibit human immunodeficiency virus infection via inhibition of reverse transcriptase.
Analogues of 2',5'-oligoadenylates (2-5A), the cordycepin (3'-deoxyadenosine) core trimer (Co3) and its 5'-monophosphate derivative (pCo3), were shown to display pronounced anti-human immunodeficiency virus type 1 (HIV-1) activity in vitro. Treatment of HIV-1 infected H9 cells with 1 microM Co3 or pCo3 resulted in an almost 100% inhibition of virus production. The compounds were encapsulated in liposomes targeted by antibodies specific for the T-cell receptor molecule CD3. Substitution of one or two cordycepin units in Co3 or pCo3 decreased the antiviral activity of the compounds. pCo3 did not stimulate 2-5A-dependent ribonuclease L activity and displayed no effect on the amount of cellular…
(2'-5')Oligoadenylate and intracellular immunity against retrovirus infection.
1. 1. The double-stranded RNA-dependent 2′,5′-oligoadenylate (2–5A) synthetase/ribonuclease L (RNase L) system plays an essential role in the establishment of the antiviral state of a cell exposed to virus infection. 2. 2. Until recently, the application of 2–5A derivatives to reinforce this system seemed to be limited mainly due to the low specificity of RNase L for viral RNA. 3. 3. Two new strategies have been developed which yield a selective antiviral effect of 2–5As at least against human immunodeficiency virus-1 (HIV-1) infection: (i) an “intracellular immunization” appproach using 2-5A synthetase cDNA linked to HIV trans -acting response element (TAR) and (ii) inhibition of retrovira…