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Dual biological activity of apurinic acid on human lymphocytes: induction of interferon-gamma and protection from human immunodeficiency virus infection in vitro.

Abstract
The chemically modified DNA, apurinic acid (APA), is cytotoxic for human lymphocytes at concentrations above 100 micrograms/ml. At low concentrations (0.05-1 micrograms/ml) APA acts as an inducer interferon gamma (IFN-gamma) in lymphocytes in vitro; the maximum interferon titer of 50 units/ml was reached at 0.4 micrograms/ml. When added to the cells in combination with phytohemagglutinin A (PHA), APA displays a significant synergistic interferon-inducing ability; the maximum titer of 940 units/ml was obtained with 10 micrograms/ml of APA and 6.25 micrograms/ml of PHA. APA also proved to be an effective inhibitor of human immunodeficiency virus (HIV-1) replication in H9 cells. At a concentration of 10 micrograms/ml, APA causes a 49% inhibition of virus growth, while 20 micrograms/ml of APA are required to inhibit expression of HIV-1 p17 and p24 gag proteins by 60%. The mechanism of anti HIV-1 activity of APA likely occurs at the level of viral reverse transcriptase. This enzyme is inhibited by APA in a noncompetitive way with a Ki of 0.39 microM, while the cellular DNA polymerases alpha, beta and gamma are 140- to 300-fold less sensitive to APA.
AuthorsW E Müller, P S Sarin, D Sun, S Rossol, R Voth, M Rottmann, G Hess, K H Meyer zum Büschenfelde, H C Schröder
JournalAntiviral research (Antiviral Res) Vol. 9 Issue 3 Pg. 191-204 (Apr 1988) ISSN: 0166-3542 [Print] Netherlands
PMID2456740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Phytohemagglutinins
  • Polynucleotides
  • RNA, Messenger
  • Reverse Transcriptase Inhibitors
  • Apurinic Acid
  • Interferon-gamma
Topics
  • Apurinic Acid (pharmacology)
  • HIV (drug effects)
  • Humans
  • Interferon-gamma (biosynthesis)
  • Lymphocytes (drug effects, metabolism)
  • Phytohemagglutinins (pharmacology)
  • Polynucleotides (pharmacology)
  • RNA, Messenger (biosynthesis)
  • Reverse Transcriptase Inhibitors

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