Mechanism of inhibition of HIV-1 infection in vitro by guanine-rich oligonucleotides modified at the 5' terminal by dimethoxytrityl residue.

Abstract

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.

• Authors: H Furukawa, K Momota, T Agatsuma, I Yamamoto, S Kimura, K Shimada
• Journal: Nucleic acids research (Nucleic Acids Res) Vol. 22 Issue 25 Pg. 5621-7 (Dec 25 1994) ISSN: 0305-1048 [Print] England
• PMID: 7530843 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• HIV Envelope Protein gp120
• Oligodeoxyribonucleotides
• SA 1042
• Trityl Compounds
• HIV Reverse Transcriptase
• RNA-Directed DNA Polymerase

Topics

• Antiviral Agents
• Base Composition
• Base Sequence
• CD4-Positive T-Lymphocytes (microbiology)
• Cell Fusion
• Cell Line
• HIV Envelope Protein gp120 (metabolism)
• HIV Infections (prevention & control)
• HIV Reverse Transcriptase
• HIV-1 (growth & development)
• Humans
• Molecular Sequence Data
• Oligodeoxyribonucleotides (chemistry, therapeutic use)
• RNA-Directed DNA Polymerase (metabolism)
• Structure-Activity Relationship
• Trityl Compounds (chemistry)
• Virus Replication (drug effects)