PHOSPHATE-METHYLATED DNA AIMED AT HIV-1 RNA LOOPS AND INTEGRATED DNA INHIBITS VIRAL INFECTIVITY

被引:39
作者
BUCK, HM [1 ]
KOOLE, LH [1 ]
VANGENDEREN, MHP [1 ]
SMIT, L [1 ]
GEELEN, JLMC [1 ]
JURRIAANS, S [1 ]
GOUDSMIT, J [1 ]
机构
[1] UNIV AMSTERDAM,ACAD MED CTR,DEPT VIROL,HUMAN RETROVIRUS LAB,1105 AZ AMSTERDAM,NETHERLANDS
关键词
D O I
10.1126/science.2326635
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Phosphate-methylated DNA hybridizes strongly and specifically to natural DNA and RNA. Hybridization to single-stranded and double-stranded DNA leads to site-selective blocking of replication and transcription. Phosphate-methylated DNA was used to interrupt the life cycle of the human immunodeficiency virus type-1 (HIV-1), the causative agent of acquired immunodeficiency syndrome (AIDS). Both antisense and sense phosphate-methylated DNA 20-nucleotide oligomers, targeted at the transactivator responsive region and the primer binding site, caused complete inhibition of viral infectivity at a low concentration. Hybridization of phosphate-methylated DNA with folded and unfolded RNA was studied by ultraviolet and proton nuclear magnetic resonance spectroscopy. The combined results of hybridization studies and biological experiments suggest that the design of effective antisense phosphatemethylated DNA should focus on hairpin loop structures in the viral RNA. For sense systems, the 5′ end of the integrated viral genome is considered to be the important target site.
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页码:208 / 212
页数:5
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