Aptamers that recognize drug-resistant HIV-1 reverse transcriptase. 2008

Na Li, and Yuxuan Wang, and Arti Pothukuchy, and Angel Syrett, and Naeem Husain, and Siddharth Gopalakrisha, and Pradeepa Kosaraju, and Andrew D Ellington
Department of Chemistry and Biochemistry, Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA.

Drug-resistant variants of HIV-1 reverse transcriptase (RT) are also known to be resistant to anti-RT RNA aptamers. In order to be able to develop diagnostics and therapies that can focus on otherwise drug-resistant viruses, we have isolated two aptamers against a well-known, drug-resistant HIV-1 RT, Mutant 3 (M3) from the multidrug-resistant HIV-1 RT panel. One aptamer, M302, bound M3 but showed no significant affinity for wild-type (WT) HIV-1 RT, while another aptamer, 12.01, bound to both M3 and WT HIV-1 RTs. In contrast to all previously selected anti-RT aptamers, neither of these aptamers showed observable inhibition of either polymerase or RNase H activities. Aptamers M302 and 12.01 competed with one another for binding to M3, but they did not compete with a pseudoknot aptamer for binding to the template/primer cleft of WT HIV-1 RT. These results represent the surprising identification of an additional RNA-binding epitope on the surface of HIV-1 RT. M3 and WT HIV-1 RTs could be distinguished using an aptamer-based microarray. By probing protein conformation as a correlate to drug resistance we introduce an additional and useful measure for determining HIV-1 drug resistance.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009690 Nucleic Acid Conformation The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape. DNA Conformation,RNA Conformation,Conformation, DNA,Conformation, Nucleic Acid,Conformation, RNA,Conformations, DNA,Conformations, Nucleic Acid,Conformations, RNA,DNA Conformations,Nucleic Acid Conformations,RNA Conformations
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D052157 Aptamers, Nucleotide Nucleotide sequences, generated by iterative rounds of SELEX APTAMER TECHNIQUE, that bind to a target molecule specifically and with high affinity. DNA Aptamer,DNA Aptamers,RNA Aptamers,Rna Aptamer,Nucleotide Aptamers,Oligonucleotide Ligands, DNA,Oligonucleotide Ligands, RNA,Aptamer, DNA,Aptamer, Rna,Aptamers, DNA,Aptamers, RNA,DNA Oligonucleotide Ligands,RNA Oligonucleotide Ligands
D054303 HIV Reverse Transcriptase A reverse transcriptase encoded by the POL GENE of HIV. It is a heterodimer of 66 kDa and 51 kDa subunits that are derived from a common precursor protein. The heterodimer also includes an RNAse H activity (RIBONUCLEASE H, HUMAN IMMUNODEFICIENCY VIRUS) that plays an essential role the viral replication process. Reverse Transcriptase, HIV,Reverse Transcriptase, Human Immunodeficiency Virus,Transcriptase, HIV Reverse
D019380 Anti-HIV Agents Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS. AIDS Drug,AIDS Drugs,Anti-AIDS Agents,Anti-AIDS Drug,Anti-HIV Agent,Anti-HIV Drug,Anti-AIDS Drugs,Anti-HIV Drugs,Agent, Anti-HIV,Agents, Anti-AIDS,Agents, Anti-HIV,Anti AIDS Agents,Anti AIDS Drug,Anti AIDS Drugs,Anti HIV Agent,Anti HIV Agents,Anti HIV Drug,Anti HIV Drugs,Drug, AIDS,Drug, Anti-AIDS,Drug, Anti-HIV,Drugs, AIDS,Drugs, Anti-AIDS,Drugs, Anti-HIV
D024882 Drug Resistance, Viral The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation. Antiviral Drug Resistance,Antiviral Drug Resistances,Drug Resistances, Viral
D040081 Protein Array Analysis Ligand-binding assays that measure protein-protein, protein-small molecule, or protein-nucleic acid interactions using a very large set of capturing molecules, i.e., those attached separately on a solid support, to measure the presence or interaction of target molecules in the sample. Protein Chips,Protein Microarrays,Protein Microchips,Protein Profiling Chips,Protein Array Assay,Protein Arrays,Protein Biochips,Protein Microarray Analysis,Protein Microarray Assay,Protein Profiling Microarrays,ProteinChip,Analyses, Protein Array,Analyses, Protein Microarray,Analysis, Protein Array,Analysis, Protein Microarray,Array Analyses, Protein,Array Analysis, Protein,Array Assay, Protein,Array Assays, Protein,Array, Protein,Arrays, Protein,Assay, Protein Array,Assay, Protein Microarray,Assays, Protein Array,Assays, Protein Microarray,Biochip, Protein,Biochips, Protein,Chip, Protein,Chip, Protein Profiling,Chips, Protein,Chips, Protein Profiling,Microarray Analyses, Protein,Microarray Analysis, Protein,Microarray Assay, Protein,Microarray Assays, Protein,Microarray, Protein,Microarray, Protein Profiling,Microarrays, Protein,Microarrays, Protein Profiling,Microchip, Protein,Microchips, Protein,Profiling Chip, Protein,Profiling Chips, Protein,Profiling Microarray, Protein,Profiling Microarrays, Protein,Protein Array,Protein Array Analyses,Protein Array Assays,Protein Biochip,Protein Chip,Protein Microarray,Protein Microarray Analyses,Protein Microarray Assays,Protein Microchip,Protein Profiling Chip,Protein Profiling Microarray,ProteinChips

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