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1994-09-24
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Document 0665
DOCN M9490665
TI The 2-5A system and HIV infection.
DT 9411
AU Schroder HC; Kelve M; Muller WE; Abteilung Angewandte Molekularbiologie,
Johannes; Gutenberg-Universitat, Mainz, Germany.
SO Prog Mol Subcell Biol. 1994;14:176-97. Unique Identifier : AIDSLINE
MED/94340158
AB 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.
DE Acquired Immunodeficiency Syndrome/DRUG THERAPY/*METABOLISM Adenine
Nucleotides/*METABOLISM/TOXICITY *Antiviral Agents/TOXICITY
AIDS-Related Complex/DRUG THERAPY/METABOLISM Bacterial
Proteins/METABOLISM Cell Line Endoribonucleases/METABOLISM Enzyme
Activation Gene Products, tat/METABOLISM Human HIV Infections/DRUG
THERAPY/*METABOLISM HIV-1/DRUG EFFECTS/*PHYSIOLOGY Membrane
Proteins/METABOLISM Oligoribonucleotides/*METABOLISM/TOXICITY
Protein-Serine-Threonine Kinases/METABOLISM Support, Non-U.S. Gov't
Thionucleotides/TOXICITY 2',5'-Oligoadenylate Synthetase/METABOLISM
JOURNAL ARTICLE REVIEW REVIEW, ACADEMIC
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).