The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3'-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase.
Open accessAbstract
Resistant variants of human immunodeficiency virus type 1 (HIV-1) have been selected by limited passage in MT4 cells of both wild-type and 3'-azido-3'-deoxythymidine (AZT, zidovudine)-resistant strains with the nucleoside analogues (-)-2'-deoxy-3'-thiacytidine (3TC) and (-)-2'-deoxy-5-fluoro-3'-thiacytidine (FTC). Virus variants selected independently were crossresistant to both inhibitors. This rapid in vitro selection of resistant virus has not previously been seen with nucleoside analogues but is reminiscent of that observed with the nonnucleoside reverse transcriptase inhibitors. However, passage of wild-type virus with a combination of AZT and FTC appreciably delayed emergence of FTC-resistant virus. DNA sequence analysis of the reverse transcriptase coding region from FTC-resistant virus revealed changes at codon 184 in the highly conserved Tyr, Met, Asp, Asp (YMDD) region. When the mutation Met184-->Val was introduced into the infectious clone HXB2, this change alone accounted for the resistance (> 1000-fold) seen with both 3TC and FTC, and for a 5- to 15-fold reduction in sensitivity to their (+) enantiomers. It had no effect on susceptibility to AZT or nevirapine and minimal effect on susceptibility to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine. To determine the influence of this mutation in a background of mutations conferring resistance to AZT and nonnucleoside reverse transcriptase inhibitors, a series of HIV-1 variants were created by site-directed mutagenesis. All mutants with Met184-->Val were cross-resistant to 3TC and FTC. The Met184-->Val mutation did not influence nevirapine resistance, but resistance to AZT was suppressed. Similar suppression of AZT resistance was seen with Tyr181-->Cys. Interestingly, when both Met184-->Val and Tyr181-->Cys substitutions were present, highly resistant virus reverted to complete AZT sensitivity. Assessment of the interactive effects of multiple drug-resistance mutations may help to establish a rationale for using these drugs in the future therapy of HIV disease.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Crystal structure at 3.5 A resolution of HIV-1 reverse transcriptase complexed with an inhibitor
Kohlstaedt, L. A., Wang, J., Friedman, J. M., Rice, P. A., & Steitz, T. A. (1992) · Science · doi:10.1126/science.1377403 · Cited by 1,914
Coates, J. A., Cammack, N., Jenkinson, H. J., Jowett, A. J., Jowett, M. I., Pearson, B. A., Penn, C. R., Rouse, P. L., Viner, K. C., & Cameron, J. M. (1992) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.36.4.733 · Cited by 240
Cited by
Towards a theory of biological robustness
Kitano, H. (2007) · Molecular Systems Biology · doi:10.1038/msb4100179 · Cited by 803
A robustness-based approach to systems-oriented drug design
Kitano, H. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2195 · Cited by 488
In Vitro Antiretroviral Properties of S/GSK1349572, a Next-Generation HIV Integrase Inhibitor
Kobayashi, M., Yoshinaga, T., Seki, T., Wakasa-Morimoto, C., Brown, K. W., Ferris, R., Foster, S. A., Hazen, R. J., Miki, S., Suyama-Kagitani, A., et al. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01209-10 · Cited by 382
Gregson, J., Rhee, S. Y., Datir, R., Pillay, D., Perno, C. F., Derache, A., Shafer, R. S., & Gupta, R. K. (2020) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiz631 · Cited by 24
Byun, H., Papathanasopoulos, M. A., Steegen, K., & Basson, A. E. (2024) · Viruses · doi:10.3390/v16121888 · Cited by 5
Metadata
- Authors
- Tisdale, M., Kemp, S. D., Parry, N. R., & Larder, B. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1993-06-15
- Volume
- 90
- Issue
- 12
- Pages
- 5653-5656
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2026323517
- Cited by
- 603
- References
- 2
- FWCI
- 26.50
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
