Immune stimulation by an antisense oligomer complementary to the rev gene of HIV-1

Biochem Pharmacol. 1993 May 25;45(10):2037-43. doi: 10.1016/0006-2952(93)90014-n.


Mice developed massive splenomegaly and polyclonal hypergammaglobulinemia within 2 days after intravenous injection of a phosphorothioate oligomer that is antisense to a portion of the rev region of the HIV-1 genome. Histologic examination of spleens from injected animals showed marked expansion of a uniform-appearing population of small lymphocytes and many mitoses. Spleen mononuclear cells (SMNCs) from injected animals showed approximately a 10-fold-increased uptake of [3H]thymidine and production of IgM and IgG. Flow cytometry analysis indicated that the responding cells were predominantly B-lymphocytes. The anti-rev oligomer also was mitogenic in vitro and stimulated immunoglobulin production by normal mouse SMNCs and human peripheral blood mononuclear cells. Similar immunologic effects were observed with an anti-rev 21-mer phosphorothioate, truncated at the 3' end, but not with a 20-mer human p53 antisense phosphorothioate or a 28-mer anti-rev phosphodiester. These observations are consistent with the possibility that DNA sequences homologous to the rev gene participate in the regulation of mammalian lymphocyte activation, proliferation and maturation.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / toxicity
  • Base Sequence
  • Cell Division / drug effects
  • Cell Size / drug effects
  • DNA, Viral / analysis
  • Genes, rev / genetics*
  • HIV-1 / genetics*
  • Humans
  • Hypergammaglobulinemia / chemically induced
  • Immune System / drug effects*
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides, Antisense*
  • Oligonucleotides, Antisense / pharmacology*
  • Oligonucleotides, Antisense / toxicity
  • Species Specificity
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / embryology
  • Splenomegaly / chemically induced
  • Stimulation, Chemical
  • Thionucleotides / pharmacology*
  • Thionucleotides / toxicity


  • Antiviral Agents
  • DNA, Viral
  • Oligodeoxyribonucleotides, Antisense
  • Oligonucleotides, Antisense
  • Thionucleotides
  • NSC 624958