       Document 0748
 DOCN  M9610748
 TI    Antisense phosphorothioate oligodeoxynucleotides alter HIV type 1
       replication in cultured human macrophages and peripheral blood
       mononuclear cells.
 DT    9601
 AU    Weichold FF; Lisziewicz J; Zeman RA; Nerurkar LS; Agrawal S; Reitz MS
       Jr; Gallo RC; Laboratory of Tumor Cell Biology, National Cancer
       Institute,; National Institutes of Health, Bethesda, Maryland 20892,
       USA.
 SO    AIDS Res Hum Retroviruses. 1995 Jul;11(7):863-7. Unique Identifier :
       AIDSLINE MED/96053850
 AB    The use of antisense oligodeoxynucleotides as antiviral drugs to combat
       HIV-1 infection may offer an alternative to traditional pharmacological
       therapies. We compared the effects of two 28-mer antisense
       phosphorothioate oligodeoxynucleotides [PS-oligo(dN)] with
       non-sequence-specific controls on HIV-1 replication in long-term human
       monocyte/macrophage and PBMC cultures. The anti-rev PS-oligo(dN) was
       complementary to the messenger RNA (mRNA) sequences derived from the
       overlapping region of the HIV-1 regulatory genes tat and rev, while
       anti-gag targeted the translational initiation site of the gag mRNA. In
       vitro cytotoxicity of the PS-oligo(dN) was evaluated at concentrations
       ranging from 0.1 to 10.0 microM for a period of 20 days. Cell survival
       was 100% at 0.1 microM, but decreased to 5% at 10.0 microM in relation
       to the untreated control cultures. Our data demonstrate that replication
       of both the T cell-tropic and macrophage-tropic HIV-1 strains in primary
       cells can be inhibited by PS-oligo(dN) in a sequence-specific and
       dose-dependent manner at concentrations achievable in vivo. However, the
       sequence-dependent antiviral activity of the utilized PS-oligo(dN) was
       limited to a window of specificity at concentrations between 0.25 and
       1.0 microM.
 DE    Antiviral Agents/*PHARMACOLOGY  Cells, Cultured  Comparative Study
       Dose-Response Relationship, Drug  *Genes, rev  *Genes, tat  Human
       HIV-1/DRUG EFFECTS/GENETICS/*PHYSIOLOGY  Kinetics  Lymphocytes/*VIROLOGY
       Macrophages/*VIROLOGY  Monocytes/VIROLOGY  Oligonucleotides,
       Antisense/*PHARMACOLOGY  T-Lymphocytes/PHYSIOLOGY  Thionucleotides  Time
       Factors  Virus Replication/*DRUG EFFECTS  JOURNAL ARTICLE

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

