Sequence analysis of an HIV-1 isolate which displays unusually high-level AZT resistance in vitro
✍ Scribed by M. Muckenthaler; N. Gunkel; Dr. P. Levantis; K. Broadhurst; B. Goh; B. Colvin; G. Forster; G. G. Jackson; J. S. Oxford
- Book ID
- 102910200
- Publisher
- John Wiley and Sons
- Year
- 1992
- Tongue
- English
- Weight
- 589 KB
- Volume
- 36
- Category
- Article
- ISSN
- 0146-6615
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✦ Synopsis
Abstract
Multiple mutations in the reverse transcriptase (RT) gene were observed in a drug‐resistant isolate of human immunodeficiency virus type 1 (HIVI) from an individual having prolonged (<2 years) zidovudine (AZT) therapy. The virus replicated in PBMC′s in the presence of very high concentrations of AZT (1 25 μM). Drug‐sensitive strains were curtailed by 0.01 μM AZT.
Eleven defined mutations were observed as compared with published sequences of RT for eight strains of HIVI. Eight of these mutations were found in the domain involved in nucleotide recognition and enzyme function. Only one of the mutations, giving a Thr—Tyr change at amino acid 215, matched those previously ascribed (67,70, 215, and 219) to the generation of high‐level resistance to AZT. Therefore additional amino acid changes may have significance in the emergence of super‐resistant viruses.