1887

Abstract

Human immunodeficiency virus (HIV) reverse transcription is an error-prone process with an overall mutation rate of ∼3·4×10 per base per replication cycle. This rate can be modulated by changes in different components of the retrotranscription reaction. In particular, substitution of magnesium cations (Mg) by manganese cations (Mn) has been shown to increase misincorporation of deoxynucleotide triphosphates (dNTPs) and to alter substrate specificity. Here, it is shown that Mn also increases the HIV mutation rate . Treatment of permissive cells with Mn and subsequent HIV infection resulted in at least 6-fold and 10-fold increases in the mutant and mutation frequencies respectively, thus illustrating a further example of how to influence HIV genetic variation.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-80-8-1983
1999-08-01
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/jgv/80/8/0801983a.html?itemId=/content/journal/jgv/10.1099/0022-1317-80-8-1983&mimeType=html&fmt=ahah

References

  1. Boyer P. L., Tantillo C., Jacobo-Molina A., Nanni R. G., Ding J., Arnold E., Hughes S. H. 1994; Sensitivity of wild-type human immunodeficiency virus type 1 reverse transcriptase to dideoxynucleotides depends on template. Proceedings of the National Academy of Sciences, USA 91:4882–4886
    [Google Scholar]
  2. Cadwell R. C., Joyce G. F. 1992; Randomization of genes by PCR mutagenesis. PCR Methods and Applications 2:28–33
    [Google Scholar]
  3. Chang L. M., Bollum F. J. 1973; A comparison of associated enzyme activities in various deoxyribonucleic acid polymerases. Journal of Biological Chemistry 248:3398–3404
    [Google Scholar]
  4. Cirino N. M., Cameron C. E., Smith J. S., Rausch J. W., Roth M. J., Benkovic S. J., Le Grice S. F. J. 1995; Divalent cation modulation of the ribonuclease functions of human immunodeficiency virus reverse transcriptase. Biochemistry 34:9936–9943
    [Google Scholar]
  5. Domingo E., Holland J. J. 1997; RNA viral mutations and fitness for survival. Annual Review of Microbiology 51:151–178
    [Google Scholar]
  6. Eckert K. A., Kunkel T. A. 1993; Fidelity of DNA synthesis catalyzed by human DNA polymerase alpha and HIV-1 reverse transcriptase: effect of reaction pH. Nucleic Acids Research 21:5212–5220
    [Google Scholar]
  7. Filler A. G., Lever A. M. L. 1997; Effects of cation substitutions on reverse transcriptase and on human immunodeficiency virus production. AIDS Research and Human Retroviruses 13:291–299
    [Google Scholar]
  8. Fromant M., Blanquet S., Plateau P. 1995; Direct random mutagenesis of gene-sized DNA fragments using polymerase chain reaction. Analytical Biochemistry 224:347–353
    [Google Scholar]
  9. Gerard G. F., Grandgenett D. P. 1975; Purification and characterization of the DNA polymerase and RNase H activities in Moloney murine sarcoma–leukemia virus. Journal of Virology 15:785–797
    [Google Scholar]
  10. Goodman M. F., Keener S., Guidotti S., Branscomb E. W. 1983; On the enzymatic basis for mutagenesis by manganese. Journal of Biological Chemistry 258:3469–3475
    [Google Scholar]
  11. Lazcano A., Valverde V., Hernàndez G., Gariglio P., Fox G. E., Oro J. 1992; On the early emergence of reverse transcription: theoretical basis and experimental evidence. Journal of Molecular Evolution 35:524–536
    [Google Scholar]
  12. Leung D., Chen E., Goeddel D. 1989; A method for random mutagenesis of a defined DNA segment using a modified polymerase chain reaction. Technique 1:11–15
    [Google Scholar]
  13. Mansky L. M., Temin H. M. 1994; Lower mutation rate of bovine leukemia virus relative to that of spleen necrosis virus. Journal of Virology 68:494–499
    [Google Scholar]
  14. Mansky L. M., Temin H. M. 1995; Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase. Journal of Virology 69:5087–5094
    [Google Scholar]
  15. Martinez M. A., Sala M., Vartanian J. P., Wain-Hobson S. 1995; Reverse transcriptase and substrate dependence of the RNA hypermutagenesis reaction. Nucleic Acids Research 23:2573–2578
    [Google Scholar]
  16. Meyerhans A., Vartanian J. P., Hultgren C., Plikat U., Karlsson A., Wang L. Y., Eriksson S., Wain-Hobson S. 1994; Enhancement and restriction of HIV replication by modulation of the intracellular dNTP pool. Journal of Virology 68:535–540
    [Google Scholar]
  17. Nietfeld W., Bauer M., Fevrier M., Maier R., Holzwarth B., Frank R., Maier B., Riviere Y., Meyerhans A. 1995; Sequence constraints and recognition by cytotoxic T lymphocytes of an HLA-B27 restricted HIV-1 Gag epitope. Journal of Immunology 154:2188–2197
    [Google Scholar]
  18. Pan T., Long D. M., Uhlenbeck O. C. 1993; Title of Article. In The RNA World pp 271–302 Edited by Gesterland R. F., Atkins J. F. Plainview, NY: Cold Spring Harbor Laboratory Press;
    [Google Scholar]
  19. Perach M., Rubinek T., Hughes S. H., Hizi A. 1997; Analysis of HIV-2 RT mutants provides evidence that resistance of HIV-1 and HIV-2 RT to nucleoside analogs involves a repositioning of the template-primer. Journal of Molecular Biology 268:648–654
    [Google Scholar]
  20. Richetti M., Buc H. 1993; E . coli DNA polymerase I as a reverse transcriptase. EMBO Journal 12:387–396
    [Google Scholar]
  21. Richetti M., Buc H. 1996; A reiterative mode of DNA synthesis adopted by HIV-1 reverse transcriptase after a misincorporation. Biochemistry 35:14970–14983
    [Google Scholar]
  22. Sala M., Wain-Hobson S., Schaeffer F. 1995; Human immunodeficiency virus type 1 reverse transcriptase tG: T mispair formation on RNA and DNA templates with mismatched primers: a kinetic and thermodynamic study. EMBO Journal 14:4622–4627
    [Google Scholar]
  23. Shin Y. 1973; Interaction of metal ions with polynucleotides and related compounds. Effect of divalent metal ions on the conformational changes of polyribonucleotides. Biopolymers 12:2459–2475
    [Google Scholar]
  24. Sirover M. A., Loeb L. A. 1977; On the fidelity of DNA replication. Effect of metal activator during synthesis with avian myeloblastosis virus DNA polymerase. Journal of Biological Chemistry 252:3605–3610
    [Google Scholar]
  25. Valverde-Garduño V., Gariglio P., Gutiérrez L. 1998; Functional analysis of HIV-1 reverse transcriptase motif C: site-directed mutagenesis and metal cation interaction. Journal of Molecular Evolution 47:73–80
    [Google Scholar]
  26. Vamvakopoulos N. C., Vournakis J. N., Marcus S. L. 1977; The effect of magnesium and manganese ions on the structure and template activity for reverse transcriptase of polyribocytidylate and its 2′-O-methyl derivative. Nucleic Acids Research 4:3589–3597
    [Google Scholar]
  27. Van Beveren C., Goulian M. 1979; Optimal conditions for synthesis of long complementary DNA product with Moloney murine leukemia virus. Journal of Virology 30:951–954
    [Google Scholar]
  28. Vartanian J. P., Meyerhans A., Sala M., Wain-Hobson S. 1994; G→A hypermutation of the HIV-1 genome: evidence for dCTP pool imbalance during reverse transcription. Proceedings of the National Academy of Sciences, USA 91:3092–3096
    [Google Scholar]
  29. Vartanian J. P., Henry M., Wain-Hobson S. 1996; Hypermutagenic PCR involving all four transitions and a sizeable proportion of transversions. Nucleic Acids Research 24:2627–2631
    [Google Scholar]
  30. Vartanian J. P., Plikat U., Maheux R., Guillemot L., Meyerhans A., Wain-Hobson S. 1997; HIV genetic variability is directed and restricted by DNA precursor availability. Journal of Molecular Biology 270:139–151
    [Google Scholar]
  31. Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M. 1985; Nucleotide sequence of the AIDS virus, LAV. Cell 40:9–17
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-80-8-1983
Loading
/content/journal/jgv/10.1099/0022-1317-80-8-1983
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error