HIV Mutation Detail Information

Virus Mutation HIV Mutation M184V


Basic Characteristics of Mutations
Mutation Site M184V
Mutation Site Sentence The M184V mutation, commonly associated with resistance to NRTIs such as lamivudine and emtricitabine, and the M184V/A114S mutations, both located within the hydrophobic pocket, were shown to reduce Islatravir susceptibility in cell-based viral resistance selection assays.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region RT
Standardized Encoding Gene gag-pol:155348
Genotype/Subtype HIV-1
Viral Reference -
Functional Impact and Mechanisms
Disease HIV Infections    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment Islatravir
Location -
Literature Information
PMID 40139311
Title Kinetic Investigation of Resistance to Islatravir Conferred by Mutations in HIV-1 Reverse Transcriptase
Author Zalenski N,Meredith BR,Savoie DJ,Naas MJ,Suo DJ,Betancourt D,Seay TW,Suo Z
Journal Journal of molecular biology
Journal Info 2025 Jun 15;437(12):169100
Abstract Islatravir (EFdA) is a novel nucleoside reverse transcriptase translocation inhibitor (NRTTI) that potently blocks HIV-1 replication in vivo. Its unique structural features in contrast to nucleoside reverse transcriptase inhibitors (NRTIs), particularly the 4'-ethynyl and 3'-hydroxy groups, contribute to its high clinical potency. Once intracellularly activated to EFdA 5'-triphosphate (EFdA-TP), it competes with dATP for incorporation by HIV-1 reverse transcriptase (RT) during HIV-1 genomic replication. The 4'-ethynyl group of incorporated EFdA-MP interacts with a hydrophobic pocket of HIV-1 RT, hindering DNA translocation and terminating DNA synthesis. The M184V mutation, commonly associated with resistance to NRTIs such as lamivudine and emtricitabine, and the M184V/A114S mutations, both located within the hydrophobic pocket, were shown to reduce Islatravir susceptibility in cell-based viral resistance selection assays. To elucidate the mechanisms by which these mutations affect Islatravir inhibition, we employed pre-steady-state kinetics to investigate their impact on EFdA-TP incorporation by HIV-1 RT using both DNA and RNA templates. We found that M184V had a modest effect on EFdA-TP incorporation efficiency, increasing it 2-fold with the DNA template and decreasing it 3-fold with the RNA template. In contrast, M184V/A114S significantly inhibited EFdA-TP incorporation, reducing its incorporation efficiency 5.4-fold with the DNA template and 181-fold with the RNA template. These reductions were primarily attributable to corresponding decreases in EFdA-TP incorporation rate constants of 18-fold and 105-fold, respectively. These results suggest that, unlike FDA-approved NRTIs, the clinical efficacy of Islatravir, may not be substantially compromised by the M184V mutation alone but will be significantly reduced by the M184V/A114S mutations.
Sequence Data -
Mutation Information
Note
Basic Characteristics of Mutations
  • Mutation Site: The specific location in a gene or protein sequence where a change occurs.
  • Mutation Level: The level at which a mutation occurs, including the nucleotide or amino acid level.
  • Mutation Type: The nature of the mutation, such as missense mutation, nonsense mutation, synonymous mutation, etc.
  • Gene/Protein/Region: Refers to the specific region of the virus where the mutation occurs. Including viral genes, viral proteins, or a specific viral genome region. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main
  • Gene/Protein/Region studied in the article is marked.
  • Genotype/Subtype: Refers to the viral genotype or subtype where the mutation occurs. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main Genotype/Subtype studied in the article is marked.
  • Viral Reference: Refers to the standard virus strain used to compare and analyze viral sequences.
Functional Impact and Mechanisms
  • Disease: An abnormal physiological state with specific symptoms and signs caused by viral infection.
  • Immune: The article focuses on the study of mutations and immune.
  • Target Gene: Host genes that viral mutations may affect.
Clinical and Epidemiological Correlations
  • Clinical Information: The study is a clinical or epidemiological study and provides basic information about the population.
  • Treatment: The study mentioned a certain treatment method, such as drug resistance caused by mutations. If the study does not specifically indicate the relationship between mutations and their correspondence treatment, the main treatment studied in the article is marked.
  • Location: The source of the research data.
Literature Information
  • Sequence Data: The study provides the data accession number.