HIV Mutation Detail Information

Virus Mutation HIV Mutation M66I


Basic Characteristics of Mutations
Mutation Site M66I
Mutation Site Sentence In clinical studies with LEN, the CA resistance-associated mutations (RAMs) M66I, Q67H/K/N, K70H/N/R/S, N74D/H/K, A105S/T, and T107A/C/N/S were observed.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region CA
Standardized Encoding Gene Gag  
Genotype/Subtype HIV-1
Viral Reference -
Functional Impact and Mechanisms
Disease HIV Infections    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment Lenacapavir
Location -
Literature Information
PMID 40223733
Title Phenotypic Characterization of Replication-Impaired Lenacapavir-Resistant HIV Clinical Isolates
Author Demirdjian S,Naik V,Margot N,Falkard B,Callebaut C
Journal Journal of medical virology
Journal Info 2025 Apr;97(4):e70340
Abstract Lenacapavir (LEN) is a potent, first-in-class long-acting HIV-1 capsid (CA) inhibitor, approved for treatment of people with multi-drug resistant HIV in combination with other antiretrovirals. In clinical studies with LEN, the CA resistance-associated mutations (RAMs) M66I, Q67H/K/N, K70H/N/R/S, N74D/H/K, A105S/T, and T107A/C/N/S were observed. Phenotypic analyses of these CA mutants were possible in single cycle (SC) PhenoSense Gag-Pro assays; however, most CA mutants exhibited severely impaired replication capacity (RC), rendering phenotyping with multicycle (MC) MT-2 cytopathic assays unsuccessful for many. Here, we developed and optimized a novel MC phenotyping assay using a Rev-dependent HIV reporter cell line, Rev-CEM-Luc/GFP (RevLun assay), to further characterize these replication-impaired LEN-resistant HIV CA mutants. HIV Gag-Protease fragments from patients' plasma samples with CA RAMs and associated site-directed mutants were cloned into the pXXLAI HIV molecular clone, and replicative viral supernatants were evaluated in MT-2 and RevLun MC assays, with readouts of cytopathic effect and reporter gene expression, respectively. Viruses were also evaluated in the SC assay. We successfully phenotyped CA mutants in RevLun that were noninfectious in MT-2 assay, including clinical isolates containing M66I in various genetic contexts and combinations of LEN RAMs. LEN susceptibility in the RevLun MC assay aligned with data in the SC PhenoSense Gag-Pro assay and MC MT-2 assay when available. All viruses with LEN RAMs remained sensitive to other HIV drug classes. Using a sensitive HIV-dependent reporter system enhanced our ability to assess the phenotypes of viruses with low RC, allowing for further investigation into LEN resistance and CA RAMs.
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.