1887

Abstract

Sequential isolates of human immunodeficiency virus type 1 (HIV-1) were obtained from patients with AIDS on short and long term treatment with zidovudine (3′-azido-3′-deoxythymidine; AZT). The isolates were tested for resistance to zidovudine by monitoring the inhibition of syncytium formation, HIV-1-specific immunofluoresence and p24 production in C8166 cells. The reverse transcriptase (RT) genes of zidovudine-sensitive (< 1 μ) and -resistant (10 to 15 μ) strains were amplified using the polymerase chain reaction and the products were sequenced directly. The predicted amino acid sequences of the RTs of zidovudine-sensitive and-resistant isolates showed 95 to 97% identity to the corresponding sequence of HIV-1 which was used as a reference. Amino acid changes at positions 41, 67, 70, 215 and 219 which are known to be associated with zidovudine resistance were present in some, but not all isolates exhibiting zidovudine resistance . This indicates that mutations in the RT of HIV-1, other than those already identified, may be involved in conferring resistance to zidovudine.

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1993-02-01
2021-10-24
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References

  1. Ball J. K., Desselberger U. 1992; Incorporation of single stranded DNA binding protein early in PCR product sequencing reactions prevents enzyme pausing. Analytical Biochemistry (in press)
    [Google Scholar]
  2. Boucher C. A., Tersmette M., Lange J. M., Kellam P., De Goede R. E., Mulder J. W., Darby G., Goudsmit J., Larder B. A. 1990; Zidovudine sensitivity of human immunodeficiency viruses from high-risk, symptom-free individuals during therapy. Lancet 336:585–590
    [Google Scholar]
  3. Briesen H., Becker W. B., Henco K., Helm E. B., Gelderblom H., R Brede H. D., Rubsamen-Waigmann H. D. 1987; Isolation, frequency and growth properties of HIV variants: multiple simultaneous variants in a patient demonstrated by molecular cloning. Journal of Medical Virology 23:51–66
    [Google Scholar]
  4. Fischl M. A., Richman D. D., Grieco M. H., Gottlob M. S., Volberding P. A., Laskin D. L., Leedom J. M., Groopman J. E., Mildvan D., Schooley R. T., Jackson G. G., Durack D. T., King D. 1987; The efficacy of azidothymidine (AZT) in ºhe treatment of patients with AIDS and AIDS-related complex. N€W England Journal of Medicine 317:185–191
    [Google Scholar]
  5. Furman P. A., Fyfe J. A., St Clair M. H., Weinhold K., Rideout J. L., Freeman G. A., Lehrman S. N., Bolognesi D. P., Broder S., Mttstiya H., Barry D. W. 1986; Phosphorylation of 3′ azido-3-deoxythymidine and selective interaction of the 5'-tri-phosphate with human immunodeficiency vims reverse transcriptase. Proceedings of the National Academy of Sciences, U.S.A 838333–8337
    [Google Scholar]
  6. Kohlstaedt L. A., Wang J., Friedman J. M., Rice P. A., Steitz T. A. 1992; Crystal structure at 3—5 Å resolution of HIV-1 reverse transcriptase complexed with an inhibitor. Science 256:1783–1790
    [Google Scholar]
  7. Larder B. A., Kemp S. D. 1989; Multiple mutations in HIV-1 reverse transcriptase confer high level resistance to zidovudine (AZT). Science 246:1155–1158
    [Google Scholar]
  8. Larder B. A., Darby G., Richman D. D. 1989; HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science 243:1731–1734
    [Google Scholar]
  9. Larder B. A., Kjellam P., Kemp S. D. 1991; Zidovudine resistance predicted by direct detection of mutations in DNA from HIV-infected lymphocytes. AIDS 5:137–144
    [Google Scholar]
  10. Mitsuya H., Weinhold K. J., Furman P. A., St Clair M. H., Lehrman S. F., Gallo R. C., Bolognesi D., Barry D. W., Broder S. 1985; 3-Azido-3-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type 3/lymphadenopathy-associated virus in vitro. Proceedings of the National Academy of Sciences, U.S.A 82:7096–7100
    [Google Scholar]
  11. Ratner L., Haseltine W. A., Patarca R., Livak K. J., Starcich B., Josephs S. F., Doran E. R., Rafalski J. A., Whitehorn E. A., Baumeistek K., Ivanoff L., Petteway S. R., Pearson M. L., Lautenberger J. A., Papas T. S., Ghrayeb J., Chang N. T., Gallo R. C., Wong-Staal F. 1985; Complete nucleotide sequence of the AIDS virus, HTLV-III. Nature, London 313:277–283
    [Google Scholar]
  12. Rooke R., Tremblay M., Soudeyns H., De Stephano L., Yao X. J., Fanning M., Montaner J. S. G., Shaughnessy M., Gelmon K., Tsoukas C., Gill J., Ruedy J., Wainberg M. A. 1989; Isolation of drug resistant variants of HIV-1 from patents on long term zidovudine therapy. AIDS 3:411–415
    [Google Scholar]
  13. Sanchez-Pescador P., Power M. P., Barr P. J., Steimer K. S., Stempien M. M., Brown-Shimer S. L., Gee W. W., ReNard A., Randolph A., Levy J. A., Dina D., Luciw P. A. 1985; Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-2). Science 221:484–492
    [Google Scholar]
  14. St Clair M. H., Martin J. L., Tudor-Williams G., Bach M. C., Vavro C. L., King D. M., Kellam P., Kemp S. P., Larder B. A. 1991; Resistance to ddl and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase. Science 253:1557–1559
    [Google Scholar]
  15. Ulrich P. P., Busch M. P., El-Beik T., Shiota J., Vennari J., Shriver K., Vyas G. N. 1988; Assessment of human immune-deficiency virus expression in co-cultures of peripheral blood mononuclear cells from healthy seropositive subjects. Journal of Medical Virology 25:1–10
    [Google Scholar]
  16. Winship P. R. 1989; An improved method for directly sequencing PCR amplified material using DMSO. Nucleic Acids Research 17:1266
    [Google Scholar]
  17. Yarchoan R., Mitsuya H., Thomas V. R., Pluda J. M., Hartman R. N., Perrno F. C., Marczyk S. K., Allain P. J., Johns G. D., Broder S. 1989; In vivo activity against HIV and favorable toxicity profile of 2', 3'-dideoxyinosine. Science 245:412–415
    [Google Scholar]
  18. Zimmerman T. P., Mahony W. B., Prus K. L. 1987; 3'-Azido-3'-deoxythymidine: an unusual nucleotide analogue that permeates the membrane of human erythrocytes and lymphocytes by nonfacilitated diffusion. Journal of Biological Chemistry 262:5748–5754
    [Google Scholar]
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