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Nucleic Acids Research, 1994, Vol. 22, No. 25 5621-5627
© 1994

Articles

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

Hidehiko Furukawa*, Kenji Momota, Toshinori Agatsuma, Ikue Yamamoto, Satoshi Kimura and Kaoru Shimada

Biological Research Laboratories, Sankyo Co. Ltd, Medical Science Institute of University of Tokyo 1-2-58 Hiromach, Shinagawa, Tokyo 140, Japan

*To whom correspondence should be addressed

Received September 6, 1994. Revised November 18, 1994. Accepted November 14, 1994.

Oligodeoxyrlbonucleotides (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 µg/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 syncytlum formation between chronically infected cells and CD4 positive uninfected cells. Furthermore, the oligomer interfered the interaction of purified gpl2O to the CD4 receptor. By contrast, SA-1 042 had no inhibitory etfect on chronically HIVinfected cells. These results strongly suggest that the DmTr-ODNs with appropriate base sequences antagonize H1V-1 Infection during the stage of virus — cell interaction.


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