       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).

