Abstract: Leu74Val, Glu89Gly, Tyr183Phe, Met184Lue, Met184Val and Met184Ile) show enhanced accuracy of DNA synthesis relative to wild-type HIV-1 RT (as evident from a reduction in the capacity to introduce mispairs and to elongate them).
Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients.
Abstract: The M184V mutation, that confers high and low-level resistance to 3TC and ddC, respectively, can restore sensitivity to AZT when introduced into RT against a background of AZT-resistance.
Abstract: The combination of M184V and E89G displayed synergistic resistance against ddCTP but not 3TCTP, while viruses containing only E89G were highly resistant to 3TCTP and displayed low-level resistance to ddCTP.
Abstract: To explore this subject further, we have used an endogenous RT reaction to study mutated viruses containing M184V alone or M184V combined with each of the K65R, E89G or both the M41L an
The impact of multidideoxynucleoside resistance-conferring mutations in human immunodeficiency virus type 1 reverse transcriptase on polymerase fidelity and error specificity.
Abstract: The nucleoside analog resistance mutations in the beta9-beta10 (M184V) and the beta5a (E89G) strands of HIV-1 RT were previously shown to increase the fidelity of deoxynucleoside triphosphate insertion.
Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients.
Abstract: Therefore, the overall polymerase fidelities of wild-type, E89G, M184V, and E89G/M184V HIV-1 RTs are similar (less than twofold differences) for DNA-dependent DNA synthesis.
Abstract: To evaluate the contribution of increased nucleotide insertion and primer extension fidelities on the overall error rate of HIV-1 RT, we have measured the impact of two such mutations, E89G and M184V, on DNA copying fidelity in an M13 phage-based forward mutation assay.
Abstract: Using this assay, we observed mutation frequencies of 8.60 x 10(-3), 6.26 x 10(-3), 5.53 x 10(-3), and 12.30 x 10(-3) for wild-type, E89G, M
The influence of 3TC resistance mutation M184I on the fidelity and error specificity of human immunodeficiency virus type 1 reverse transcriptase.
Abstract: First, variants of HIV with the M184I substitution appear transiently, followed by viruses containing the M184V substitution, which persist and become the dominant variant for the duration of therapy.
Abstract: This represents a 4-fold increase in fidelity over wild-type HIV-1Hxb2RT (7.0 x 10(-5) per nucleotide) and a 2.5-fold increase in fidelity over the M184V variant (4.3 x 10(-5) per nucleotide).
Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients.
Abstract: M184V per se is not expected to compromise subsequent treatment with NRTI such as didanosine-stavudine or combinations containing abacavir.
Abstract: OBJECTIVE: To investigate the prevalence and magnitude of M184V-mediated changes in susceptibility to zalcitabine, didanosine, stavudine and abacavir (1592U89 succinate) in a cohort of lamivudine-treated patients.
Abstract: There were no other genotypic changes in addition to M184V known to be associated with abacavir resistance.
Kinetics of Archived M184V Mutation in Treatment-Experienced Virally Suppressed HIV-Infected Patients.
PMID: 9643373
1998
AIDS research and human retroviruses
Abstract: In contrast, M184V-containing HIV first showed escape between days 25 and 32 and sequence analysis revealed an aspartate-to-tyrosine change at amino acid 5 in V3 (N5Y; AAC --> TAC) in two of six clones at day 36 and in five of five clones at day 55.
Abstract: In contrast, the N5Y substitution seen with M184V-containing HIV-1 is an A --> T transversion in V3.
Abstract: The M184V substitution in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase
Abstract: The escape mutation in the wild type is consistent with the G --> A hypermutation observed in wild-type HIV-1, recently shown to cause an initial M184I change (before M184V) in 3TC-treated patients.
Loss of polymerase activity due to Tyr to Phe substitution in the YMDD motif of human immunodeficiency virus type-1 reverse transcriptase is compensated by Met to Val substitution within the same motif.
Abstract: Curiously, the double mutant did not exhibit any synergistic effect in regard to fidelity of DNA synthesis as might be expected since both the single mutations (Y183F, M184V) exhibited enhanced fidelity compared to the wild-type enzyme.
Human immunodeficiency virus type 1 reverse transcriptase expressing the K70E mutation exhibits a decrease in specific activity and processivity.
Abstract: In single-cycle processivity studies, the M184V mutant was, as expected, notably impaired.
Abstract: The Ki values for the K65R mutant were increased from wild-type by 2-5-fold against a variety of inhibitors, whereas the Ki values for the M184V mutant were increased 12-fold specifically for 2', 3'-dideoxy-3'-thiacytidine (3TC) triphosphate.
Abstract: To further investigate the molecular mechanisms involved in the resistance to PMEA, we cloned, expressed, and purified HIV-1 RT enzymes carrying either the K65R or K70E and, for comparison, the M184V mutation.
Dominance of the E89G substitution in HIV-1 reverse transcriptase in regard to increased polymerase processivity and patterns of pausing.
PMID: 9705331
1998
The Journal of biological chemistry
Abstract: Consistent with these observations, and from a mechanistic standpoint, both E89G-containing as well as doubly mutated RT had decreased dissociation constants from a complex consisting of RT and template-primer, in comparison with either wt RT or M184V-containing RT.
Abstract: In addition, certain mutations in RT that confer resistance to nucleoside analogs, such as M184V, are located near the polymerase active site.
Abstract: Similar findings were obtained with the doubly mutated RT, although enzyme containing only the M184V mutation had lower processivity than wt.
HIV mutation literature information.
PMID: 
1998
Nucleic acids research
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