Immune stimulation by an antisense oligomer complementary to the rev gene of HIV-1.
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.
Branda
R F
RF
Department of Medicine, University of Vermont, Burlington 05405.
Moore
A L
AL
Mathews
L
L
McCormack
J J
JJ
Zon
G
G
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000633:toxicity; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D004279:DNA, Viral / Q000032:analysis; D015757:Genes, rev / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D006942:Hypergammaglobulinemia / Q000139:chemically induced; D007107:Immune System / Q000187:drug effects*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D020319:Oligodeoxyribonucleotides, Antisense; D016376:Oligonucleotides, Antisense / Q000494:pharmacology* / Q000633:toxicity; D013045:Species Specificity; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D013163:Splenomegaly / Q000139:chemically induced; D013268:Stimulation, Chemical; D013873:Thionucleotides / Q000494:pharmacology* / Q000633:toxicity
D000998:Antiviral Agents; D004279:DNA, Viral; D020319:Oligodeoxyribonucleotides, Antisense; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; C081550:NSC 624958