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Restriction and enhancement of human immunodeficiency virus type 1 replication by modulation of intracellular deoxynucleoside triphosphate pools.
Abstract
Human immunodeficiency virus type 1 (HIV-1) replication is shown to be sensitive to the intracellular concentration of deoxynucleoside triphosphate substrates. Addition of thymidine to established cell lines resulted in a dramatic reduction of virus production. The effect could be substantially alleviated by addition of deoxycytidine, which, alone, enhanced viral titers by a factor of 2 to 3. Hydroxyurea treatment abolished HIV-1 replication in peripheral blood mononuclear cells and could be reversed by deoxyadenosine. These data show that HIV-1 replication occurs under suboptimal DNA precursor conditions.
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- Bebenek K, Roberts JD, Kunkel TA. The effects of dNTP pool imbalances on frameshift fidelity during DNA replication. J Biol Chem. 1992 Feb 25;267(6):3589–3596. [PubMed] [Google Scholar]
- Belt RJ, Haas CD, Kennedy J, Taylor S. Studies of hydroxyurea administered by continuous infusion: toxicity, pharmacokinetics, and cell synchronization. Cancer. 1980 Aug 1;46(3):455–462. [PubMed] [Google Scholar]
- Blumenreich MS, Woodcock TM, Andreeff M, Hiddemann W, Chou TC, Vale K, O'Hehir M, Clarkson BD, Young CW. Effect of very high-dose thymidine infusions on leukemia and lymphoma patients. Cancer Res. 1984 May;44(5):2203–2207. [PubMed] [Google Scholar]
- Bowerman B, Brown PO, Bishop JM, Varmus HE. A nucleoprotein complex mediates the integration of retroviral DNA. Genes Dev. 1989 Apr;3(4):469–478. [PubMed] [Google Scholar]
- Bradley MO, Sharkey NA. Mutagenicity of thymidine to cultured Chinese hamster cells. Nature. 1978 Aug 10;274(5671):607–608. [PubMed] [Google Scholar]
- Bray G, Brent TP. Deoxyribonucleoside 5'-triphosphate pool fluctuations during the mammalian cell cycle. Biochim Biophys Acta. 1972 May 10;269(2):184–191. [PubMed] [Google Scholar]
- Chen TR. In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain. Exp Cell Res. 1977 Feb;104(2):255–262. [PubMed] [Google Scholar]
- Cohen A, Barankiewicz J, Lederman HM, Gelfand EW. Purine and pyrimidine metabolism in human T lymphocytes. Regulation of deoxyribonucleotide metabolism. J Biol Chem. 1983 Oct 25;258(20):12334–12340. [PubMed] [Google Scholar]
- Collins A, Oates DJ. Hydroxyurea: effects on deoxyribonucleotide pool sizes correlated with effects on DNA repair in mammalian cells. Eur J Biochem. 1987 Dec 1;169(2):299–305. [PubMed] [Google Scholar]
- Dahbo Y, Eriksson S. On the mechanism of deoxyribonucleoside toxicity in human T-lymphoblastoid cells. Reversal of growth inhibition by addition of cytidine. Eur J Biochem. 1985 Aug 1;150(3):429–434. [PubMed] [Google Scholar]
- Grewe C, Beck A, Gelderblom HR. HIV: early virus-cell interactions. J Acquir Immune Defic Syndr. 1990;3(10):965–974. [PubMed] [Google Scholar]
- Howell SB, Chu B, Mendelsohn J, Carson DA, Kung FH, Seegmiller JE. Thymidine as a chemotherapeutic agent: pharmacologic, cytokinetic, and biochemical studies in a patient with T-cell acute lymphocytic leukemia. J Natl Cancer Inst. 1980 Aug;65(2):277–284. [PubMed] [Google Scholar]
- Hübner A, Kruhoffer M, Grosse F, Krauss G. Fidelity of human immunodeficiency virus type I reverse transcriptase in copying natural RNA. J Mol Biol. 1992 Feb 5;223(3):595–600. [PubMed] [Google Scholar]
- Ji JP, Mathews CK. Analysis of mutagenesis induced by a thermolabile T4 phage deoxycytidylate hydroxymethylase suggests localized deoxyribonucleotide pool imbalance. Mol Gen Genet. 1991 Apr;226(1-2):257–264. [PubMed] [Google Scholar]
- Kennedy BJ. The evolution of hydroxyurea therapy in chronic myelogenous leukemia. Semin Oncol. 1992 Jun;19(3 Suppl 9):21–26. [PubMed] [Google Scholar]
- Kresnak MT, Davidson RL. Thymidine-induced mutations in mammalian cells: sequence specificity and implications for mutagenesis in vivo. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2829–2833. [PMC free article] [PubMed] [Google Scholar]
- Kunkel TA. Biological asymmetries and the fidelity of eukaryotic DNA replication. Bioessays. 1992 May;14(5):303–308. [PubMed] [Google Scholar]
- Kunkel TA, Silber JR, Loeb LA. The mutagenic effect of deoxynucleotide substrate imbalances during DNA synthesis with mammalian DNA polymerases. Mutat Res. 1982 Jun;94(2):413–419. [PubMed] [Google Scholar]
- Kunz BA, Kohalmi SE. Modulation of mutagenesis by deoxyribonucleotide levels. Annu Rev Genet. 1991;25:339–359. [PubMed] [Google Scholar]
- Layne SP, Merges MJ, Dembo M, Spouge JL, Conley SR, Moore JP, Raina JL, Renz H, Gelderblom HR, Nara PL. Factors underlying spontaneous inactivation and susceptibility to neutralization of human immunodeficiency virus. Virology. 1992 Aug;189(2):695–714. [PubMed] [Google Scholar]
- Lemaître M, Henin Y, Destouesse F, Ferrieux C, Montagnier L, Blanchard A. Role of mycoplasma infection in the cytopathic effect induced by human immunodeficiency virus type 1 in infected cell lines. Infect Immun. 1992 Mar;60(3):742–748. [PMC free article] [PubMed] [Google Scholar]
- Lo SC, Tsai S, Benish JR, Shih JW, Wear DJ, Wong DM. Enhancement of HIV-1 cytocidal effects in CD4+ lymphocytes by the AIDS-associated mycoplasma. Science. 1991 Mar 1;251(4997):1074–1076. [PubMed] [Google Scholar]
- Mathews CK, Ji J. DNA precursor asymmetries, replication fidelity, and variable genome evolution. Bioessays. 1992 May;14(5):295–301. [PubMed] [Google Scholar]
- McCormick PJ, Danhauser LL, Rustum YM, Bertram JS. Changes in ribo- and deoxyribonucleoside triphosphate pools within the cell cycle of a synchronized mouse fibroblast cell line. Biochim Biophys Acta. 1983 Mar 15;756(1):36–40. [PubMed] [Google Scholar]
- Meuth M. The molecular basis of mutations induced by deoxyribonucleoside triphosphate pool imbalances in mammalian cells. Exp Cell Res. 1989 Apr;181(2):305–316. [PubMed] [Google Scholar]
- Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. [PubMed] [Google Scholar]
- Mun BJ, Mathews CK. Cell cycle-dependent variations in deoxyribonucleotide metabolism among Chinese hamster cell lines bearing the Thy- mutator phenotype. Mol Cell Biol. 1991 Jan;11(1):20–26. [PMC free article] [PubMed] [Google Scholar]
- Nicander B, Reichard P. Dynamics of pyrimidine deoxynucleoside triphosphate pools in relationship to DNA synthesis in 3T6 mouse fibroblasts. Proc Natl Acad Sci U S A. 1983 Mar;80(5):1347–1351. [PMC free article] [PubMed] [Google Scholar]
- Peden K, Emerman M, Montagnier L. Changes in growth properties on passage in tissue culture of viruses derived from infectious molecular clones of HIV-1LAI, HIV-1MAL, and HIV-1ELI. Virology. 1991 Dec;185(2):661–672. [PubMed] [Google Scholar]
- Phear G, Nalbantoglu J, Meuth M. Next-nucleotide effects in mutations driven by DNA precursor pool imbalances at the aprt locus of Chinese hamster ovary cells. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4450–4454. [PMC free article] [PubMed] [Google Scholar]
- Reichard P. Interactions between deoxyribonucleotide and DNA synthesis. Annu Rev Biochem. 1988;57:349–374. [PubMed] [Google Scholar]
- Sinigaglia F, Talmadge KW. Inhibition of [3H]thymidine incorporation by Mycoplasma arginini-infected cells due to enzymatic cleavage of the nucleoside. Eur J Immunol. 1985 Jul;15(7):692–696. [PubMed] [Google Scholar]
- Slabaugh MB, Howell ML, Wang Y, Mathews CK. Deoxyadenosine reverses hydroxyurea inhibition of vaccinia virus growth. J Virol. 1991 May;65(5):2290–2298. [PMC free article] [PubMed] [Google Scholar]
- Tattersall MH, Ganeshaguru K, Hoffbrand AV. The effect of external deoxyribonucleosides on deoxyribonucleoside triphosphate concentrations in human lymphocytes. Biochem Pharmacol. 1975 Aug 15;24(16):1495–1498. [PubMed] [Google Scholar]
- Timson J. Hydroxyurea: comparison of cytotoxic and antimitotic activities against human lymphocytes in vitro. Br J Cancer. 1969 Jun;23(2):337–339. [PMC free article] [PubMed] [Google Scholar]
- Tyrsted G. Effect of hydroxyurea and 5-fluorodeoxyuridine on deoxyribonucleoside triphosphate pools early in phytohemagglutinin-stimulated human lymphocytes. Biochem Pharmacol. 1982 Oct 1;31(19):3107–3113. [PubMed] [Google Scholar]
- Vartanian JP, Meyerhans A, Asjö B, Wain-Hobson S. Selection, recombination, and G----A hypermutation of human immunodeficiency virus type 1 genomes. J Virol. 1991 Apr;65(4):1779–1788. [PMC free article] [PubMed] [Google Scholar]
- Wain-Hobson S, Vartanian JP, Henry M, Chenciner N, Cheynier R, Delassus S, Martins LP, Sala M, Nugeyre MT, Guétard D, et al. LAV revisited: origins of the early HIV-1 isolates from Institut Pasteur. Science. 1991 May 17;252(5008):961–965. [PubMed] [Google Scholar]
- Wolfe KH. Mammalian DNA replication: mutation biases and the mutation rate. J Theor Biol. 1991 Apr 21;149(4):441–451. [PubMed] [Google Scholar]
- Wolfe KH, Sharp PM, Li WH. Mutation rates differ among regions of the mammalian genome. Nature. 1989 Jan 19;337(6204):283–285. [PubMed] [Google Scholar]
- Yoshioka A, Tanaka S, Hiraoka O, Koyama Y, Hirota Y, Ayusawa D, Seno T, Garrett C, Wataya Y. Deoxyribonucleoside triphosphate imbalance. 5-Fluorodeoxyuridine-induced DNA double strand breaks in mouse FM3A cells and the mechanism of cell death. J Biol Chem. 1987 Jun 15;262(17):8235–8241. [PubMed] [Google Scholar]
- Zack JA, Arrigo SJ, Weitsman SR, Go AS, Haislip A, Chen IS. HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell. 1990 Apr 20;61(2):213–222. [PubMed] [Google Scholar]
- Zack JA, Haislip AM, Krogstad P, Chen IS. Incompletely reverse-transcribed human immunodeficiency virus type 1 genomes in quiescent cells can function as intermediates in the retroviral life cycle. J Virol. 1992 Mar;66(3):1717–1725. [PMC free article] [PubMed] [Google Scholar]
- Zaharko DS, Bolten BJ, Chiuten D, Wiernik PH. Pharmacokinetic studies during phase I trials of high-dose thymidine infusions. Cancer Res. 1979 Dec;39(12):4777–4781. [PubMed] [Google Scholar]