Document 0205
 DOCN  M9610205
 TI    Inhibition of the integrase of human immunodeficiency virus (HIV) type 1
       by anti-HIV plant proteins MAP30 and GAP31.
 DT    9601
 AU    Lee-Huang S; Huang PL; Huang PL; Bourinbaiar AS; Chen HC; Kung HF;
       Department of Biochemistry, New York University School of; Medicine, NY
       10016, USA.
 SO    Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8818-22. Unique Identifier
       : AIDSLINE MED/96004630
 AB    MAP30 (Momordica anti-HIV protein of 30 kDa) and GAP31 (Gelonium
       anti-HIV protein of 31 kDa) are anti-HIV plant proteins that we have
       identified, purified, and cloned from the medicinal plants Momordica
       charantia and Gelonium multiflorum. These antiviral agents are capable
       of inhibiting infection of HIV type 1 (HIV-1) in T lymphocytes and
       monocytes as well as replication of the virus in already-infected cells.
       They are not toxic to normal uninfected cells because they are unable to
       enter healthy cells. MAP30 and GAP31 also possess an N-glycosidase
       activity on 28S ribosomal RNA and a topological activity on plasmid and
       viral DNAs including HIV-1 long terminal repeats (LTRs). LTRs are
       essential sites for integration of viral DNA into the host genome by
       viral integrase. We therefore investigated the effect of MAP30 and GAP31
       on HIV-1 integrase. We report that both of these antiviral agents
       exhibit dose-dependent inhibition of HIV-1 integrase. Inhibition was
       observed in all of the three specific reactions catalyzed by the
       integrase, namely, 3' processing (specific cleavage of the dinucleotide
       GT from the viral substrate), strand transfer (integration), and
       disintegration (the reversal of strand transfer). Inhibition was studied
       by using oligonucleotide substrates with sequences corresponding to the
       U3 and U5 regions of HIV LTR. In the presence of 20 ng of viral
       substrate, 50 ng of target substrate, and 4 microM integrase, total
       inhibition was achieved at equimolar concentrations of the integrase and
       the antiviral proteins, with EC50 values of about 1 microM. Integration
       of viral DNA into the host chromosome is a vital step in the replicative
       cycle of retroviruses, including the AIDS virus. The inhibition of HIV-1
       integrase by MAP30 and GAP31 suggests that impediment of viral DNA
       integration may play a key role in the anti-HIV activity of these plant
       proteins.
 DE    Antiviral Agents/*PHARMACOLOGY  Base Sequence  Comparative Study  DNA
       Nucleotidyltransferases/*ANTAGONISTS & INHIB/METABOLISM  HIV Long
       Terminal Repeat  HIV-1/*ENZYMOLOGY/GENETICS  Molecular Sequence Data
       Nucleic Acid Conformation  Plant Proteins/*PHARMACOLOGY  Recombinant
       Proteins/PHARMACOLOGY  Substrate Specificity  Support, U.S. Gov't,
       P.H.S.  Virus Integration/*DRUG EFFECTS  JOURNAL ARTICLE

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       protected by Copyright Law (Title 17, U.S.Code).