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.
Department of Medicine, University of Vermont, Burlington 05405.
R F
RF
Branda
A L
AL
Moore
L
L
Mathews
J J
JJ
McCormack
G
G
Zon
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