Mechanism of inhibition of HIV-1 infection in vitro by guanine-rich oligonucleotides modified at the 5' terminal by dimethoxytrityl residue.
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.
Furukawa
H
H
Biological Research Laboratories, Sankyo Co. Ltd, Medical Science Institute of University of Tokyo, Japan.
Momota
K
K
Agatsuma
T
T
Yamamoto
I
I
Kimura
S
S
Shimada
K
K
D000998:Antiviral Agents; D001482:Base Composition; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology; D002459:Cell Fusion; D002460:Cell Line; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000517:prevention & control*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000627:therapeutic use*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D013329:Structure-Activity Relationship; D014320:Triphenylmethyl Compounds / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D015699:HIV Envelope Protein gp120; D009838:Oligodeoxyribonucleotides; C107784:SA 1042; D014320:Triphenylmethyl Compounds; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase