HIV Mutation Detail Information

Virus Mutation HIV Mutation A19E


Basic Characteristics of Mutations
Mutation Site A19E
Mutation Site Sentence Proteins defective for both CD4 downregulation and tetherin counteraction (i.e. less than the 81% cutoff for tetherin and 73.7% for CD4) contained a frame-shift (n = 1), an A19E change in the transmembrane domain (n = 1), mutations of the highly conserved regions just prior to (E29K;n = 2) and within (II43,46SL, R49G, R49T;n = 3) the first alpha-helix, and in the DSGNES hinge region between the two cytoplasmic alpha helices (D52V, SN53,55RH, S53N, E58K;n = 4), which contains two phosphorylated serines essential for interactions with the E3 ubiquitin ligase complex SCFbeta-TrCP, central to Vpu's function.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region Vpu
Standardized Encoding Gene Vpu  
Genotype/Subtype HIV-1 B
Viral Reference NL4.3
Functional Impact and Mechanisms
Disease HIV Infections    
Immune Y
Target Gene CD8A    CD4    BST2    NFKB1   
Clinical and Epidemiological Correlations
Clinical Information Y
Treatment -
Location USA
Literature Information
PMID 24465210
Title Preservation of tetherin and CD4 counter-activities in circulating Vpu alleles despite extensive sequence variation within HIV-1 infected individuals
Author Pickering S,Hue S,Kim EY,Reddy S,Wolinsky SM,Neil SJ
Journal PLoS pathogens
Journal Info 2014 Jan;10(1):e1003895
Abstract The HIV-1 Vpu protein is expressed from a bi-cistronic message late in the viral life cycle. It functions during viral assembly to maximise infectious virus release by targeting CD4 for proteosomal degradation and counteracting the antiviral protein tetherin (BST2/CD317). Single genome analysis of vpu repertoires throughout infection in 14 individuals infected with HIV-1 clade B revealed extensive amino acid diversity of the Vpu protein. For the most part, this variation in Vpu increases over the course of infection and is associated with predicted epitopes of the individual's MHC class I haplotype, suggesting CD8+ T cell pressure is the major driver of Vpu sequence diversity within the host. Despite this variability, the Vpu functions of targeting CD4 and counteracting both physical virus restriction and NF-kappaB activation by tetherin are rigorously maintained throughout HIV-1 infection. Only a minority of circulating alleles bear lesions in either of these activities at any given time, suggesting functional Vpu mutants are heavily selected against even at later stages of infection. Comparison of Vpu proteins defective for one or several functions reveals novel determinants of CD4 downregulation, counteraction of tetherin restriction, and inhibition of NF-kappaB signalling. These data affirm the importance of Vpu functions for in vivo persistence of HIV-1 within infected individuals, not simply for transmission, and highlight its potential as a target for antiviral therapy.
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.