       Document 0060
 DOCN  M9550060
 TI    Mechanism of inhibition of HIV-1 infection in vitro by guanine-rich
       oligonucleotides modified at the 5' terminal by dimethoxytrityl residue.
 DT    9505
 AU    Furukawa H; Momota K; Agatsuma T; Yamamoto I; Kimura S; Shimada K;
       Biological Research Laboratories, Sankyo Co. Ltd, Medical Science;
       Institute of University of Tokyo, Japan.
 SO    Nucleic Acids Res. 1994 Dec 25;22(25):5621-7. Unique Identifier :
       AIDSLINE MED/95140624
 AB    Oligodeoxyribonucleotides (ODN) linked at their 5'-end with
       dimethoxytrityl (DmTr) residue were examined for antiviral activities
       against human immunodeficiency virus type 1 (HIV-1). We found that
       guanine-rich oligonucleotides exhibit anti-HIV activity upon 5'-end
       modification with DmTr. One oligonucleotide, DmTr-TGGGAGGTGGGTCTG
       (SA-1042), showed potent anti-HIV activity in vitro. A greater than 95%
       reduction of infectivity was observed if the cells were treated with 10
       micrograms/ml of SA-1042 at the time of viral infection, PCR analysis
       confirmed that there was a significant reduction of provirus in the
       cells exposed to virus in the presence of SA-1042. By contrast, no
       inhibition was observed if the cells were treated with the oligomer 1 h
       after virus adsorption. SA-1042 prevented syncytium formation between
       chronically infected cells and CD4 positive uninfected cells.
       Furthermore, the oligomer interfered the interaction of purified gp120
       to the CD4 receptor. By contrast, SA-1042 had no inhibitory effect on
       chronically HIV-infected cells. These results strongly suggest that the
       DMTr-ODNs with appropriate base sequences antagonize HIV-1 infection
       during the stage of virus-cell interaction.
 DE    *Antiviral Agents  Base Composition  Base Sequence  Cell Fusion  Cell
       Line  CD4-Positive T-Lymphocytes/MICROBIOLOGY  Human  HIV Envelope
       Protein gp120/METABOLISM  HIV Infections/*PREVENTION & CONTROL
       HIV-1/*GROWTH & DEVELOPMENT  Molecular Sequence Data
       Oligodeoxyribonucleotides/CHEMISTRY/*THERAPEUTIC USE  Reverse
       Transcriptase/ANTAGONISTS & INHIB  Structure-Activity Relationship
       Trityl Compounds/*CHEMISTRY  Virus Replication/*DRUG EFFECTS  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

