Document 0202
 DOCN  M9610202
 TI    Sequence-specific inhibition of human immunodeficiency virus (HIV)
       reverse transcription by antisense oligonucleotides: comparative study
       in cell-free assays and in HIV-infected cells.
 DT    9601
 AU    Bordier B; Perala-Heape M; Degols G; Lebleu B; Litvak S; Sarih-Cottin L;
       Helene C; Institut de Biochimie Cellulaire et Neurochimie, Centre
       National; de la Recherche Scientifique, Bordeaux, France.
 SO    Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9383-7. Unique Identifier :
       AIDSLINE MED/96016173
 AB    We have investigated two regions of the viral RNA of human
       immunodeficiency virus type 1 (HIV-1) as potential targets for antisense
       oligonucleotides. An oligodeoxynucleotide targeted to the U5 region of
       the viral genome was shown to block the elongation of cDNA synthesized
       by HIV-1 reverse transcriptase in vitro. This arrest of reverse
       transcription was independent of the presence of RNase H activity
       associated with the reverse transcriptase enzyme. A second
       oligodeoxynucleotide targeted to a site adjacent to the primer binding
       site inhibited reverse transcription in an RNase H-dependent manner.
       These two oligonucleotides were covalently linked to a poly(L-lysine)
       carrier and tested for their ability to inhibit HIV-1 infection in cell
       cultures. Both oligonucleotides inhibited virus production in a
       sequence- and dose-dependent manner. PCR analysis showed that they
       inhibited proviral DNA synthesis in infected cells. In contrast, an
       antisense oligonucleotide targeted to the tat sequence did not inhibit
       proviral DNA synthesis but inhibited viral production at a later step of
       virus development. These experiments show that antisense
       oligonucleotides targeted to two regions of HIV-1 viral RNA can inhibit
       the first step of viral infection--i.e., reverse transcription--and
       prevent the synthesis of proviral DNA in cell cultures.
 DE    Base Sequence  Cell Line  Cell-Free System  Comparative Study  DNA
       Primers  DNA Replication  Human  HIV-1/*ENZYMOLOGY  Kinetics  Molecular
       Sequence Data  Oligonucleotides, Antisense/*PHARMACOLOGY  Polylysine
       Polymerase Chain Reaction  Proviruses/ENZYMOLOGY  Reverse Transcriptase
       Inhibitors/*PHARMACOLOGY  Ribonuclease H, Calf Thymus/METABOLISM
       RNA-Directed DNA Polymerase/*DRUG EFFECTS  RNA,
       Viral/CHEMISTRY/METABOLISM  Support, Non-U.S. Gov't  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).