Inhibition of HIV‐1 replication by a two‐strand system (FTFOs) targeted to the polypurine tract

FEBS Letters

Hiratou, Takashi¹  Yamamoto, Naoki²  Takai, Kazuyuki¹  Takaku, Hiroshi¹  Tsukahara, Satoru¹  Miyano-Kurosaki, Naoko¹ 

[1] Department of Industrial Chemistry, Chiba Institute of Technology, Tsudanuma, Narashino, Chiba 275-0016, Japan;Department of Microbiology, Tokyo Medical and Dental University School of Medicine, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan

关键词: Triplex;    Two-strand system;    Inhibition of human immunodeficiency virus replication;    Polypurine tract;    MOLT-4 cell;    MT-4 cell;   

DOI  :  10.1016/S0014-5793(99)00932-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Reverse transcription of HIV-1 vRNA into the double-stranded DNA provirus involves initiation of plus-strand DNA synthesis at the polypurine tract (PPT) by reverse transcriptase (RT). The PPT is highly conserved among the known human immunodeficiency virus (HIV-1) strains and is a possible target for triplex formation. We show the effects of triple-helix formation by assays of primer extension inhibition in vitro, using a two-strand system (foldback triplex-forming oligonucleotides (FTFOs)) targeted to the PPT of HIV-1. The two-stranded composition of a triple-helix is thermodynamically and kinetically superior to the three-strand system. The FTFOs inhibited the RT activity in a sequence-specific manner, i.e. the triplex actually formed at the PPT and blocked the RT. The FTFOs containing the phosphorothioate groups at the antisense sequences showed greater 3′-exonuclease resistance. In HIV-1-infected MOLT-4 cells, the FTFOs containing the phosphorothioate groups at the antisense sequence sites and guanosine rich parts within the third Hoogsteen base-pairing sequence inhibit the replication of HIV-1 more effectively than the antisense oligonucleotides, indicating sequence-specific inhibition of HIV-1 replication.

【 授权许可】

Unknown