HIV Mutation Detail Information

Virus Mutation HIV Mutation K476N


Basic Characteristics of Mutations
Mutation Site K476N
Mutation Site Sentence We reported that 3'-azido-2',3'-dideoxyguanosine (3'-azido-ddG) selected for the L74V, F77L, and L214F mutations in the polymerase domain and K476N and V518I mutations in the RNase H domain of HIV-1 reverse transcriptase (RT).
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 -
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment 3'-azido-ddG
Location -
Literature Information
PMID 24211331
Title Molecular mechanism of HIV-1 resistance to 3'-azido-2',3'-dideoxyguanosine
Author Meteer JD,Schinazi RF,Mellors JW,Sluis-Cremer N
Journal Antiviral research
Journal Info 2014 Jan;101:62-7
Abstract We reported that 3'-azido-2',3'-dideoxyguanosine (3'-azido-ddG) selected for the L74V, F77L, and L214F mutations in the polymerase domain and K476N and V518I mutations in the RNase H domain of HIV-1 reverse transcriptase (RT). In this study, we have defined the molecular mechanisms of 3'-azido-ddG resistance by performing in-depth biochemical analyses of HIV-1 RT containing mutations L74V, F77L, V106I, L214F, R277K, and K476N (SGS3). The SGS3 HIV-1 RT was from a single-genome-derived full-length RT sequence obtained from 3'-azido-ddG resistant HIV-1 selected in vitro. We also analyzed two additional constructs that either lacked the L74V mutation (SGS3-L74V) or the K476N mutation (SGS3-K476N). Pre-steady-state kinetic experiments revealed that the L74V mutation allows RT to effectively discriminate between the natural nucleotide (dGTP) and 3'-azido-ddG-triphosphate (3'-azido-ddGTP). 3'-azido-ddGTP discrimination was primarily driven by a decrease in 3'-azido-ddGTP binding affinity (Kd) and not by a decreased rate of incorporation (kpol). The L74V mutation was found to severely impair RT's ability to excise the chain-terminating 3'-azido-ddG-monophosphate (3'-azido-ddGMP) moiety. However, the K476N mutation partially restored the enzyme's ability to excise 3'-azido-ddGMP on an RNA/DNA, but not on a DNA/DNA, template/primer by selectively decreasing the frequency of secondary RNase H cleavage events. Collectively, these data provide strong additional evidence that the nucleoside base structure is major determinant of HIV-1 resistance to the 3'-azido-2',3'-dideoxynucleosides.
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.