Antiviral drug resistance mutations in human immunodeficiency virus type 1 reverse transcriptase occur in specific RNA structural regions
| Autor: | C S Ramanathan, R M Lloyd, Raymond F. Schinazi, E W Taylor |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Biology
medicine.disease_cause Antiviral Agents Virus Nucleic acid secondary structure medicine Computer Simulation Pharmacology (medical) Protein secondary structure Polymerase Pharmacology Genetics Base Composition Mutation RNA-Directed DNA Polymerase RNA Drug Resistance Microbial Virology HIV Reverse Transcriptase Reverse transcriptase Infectious Diseases Models Chemical biology.protein Nucleic Acid Conformation Research Article |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 38:268-274 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.38.2.268 |
| Popis: | A statistically significant correlation exists between the locations of drug resistance mutations (DRMs) observed for various reverse transcriptase inhibitors and features of the secondary structure predicted for the RNA coding for human immunodeficiency virus type 1 reverse transcriptase. The known DRMs map onto "unstable" bases, which are predominantly nonhelical regions (i.e., loops, bulges, and bends) of the predicted RNA secondary structure, whereas codons for the key conserved residues of polymerase sequence motifs map onto "stable" paired bases involved in helical regions. On the basis of these results, we hypothesize that the secondary structure of the RNA template (in this case, the reverse transcriptase gene itself) may be a previously unrecognized factor contributing to base misincorporation errors during reverse transcription and that, rather than being randomly distributed, mutations are more likely to occur in specific regions of the genome. The results suggest that these "mutation-prone" regions can be predicted by using a standard algorithm for RNA secondary structure. |
| Databáze: | OpenAIRE |
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