HIV Mutation Detail Information

Virus Mutation HIV Mutation E28D


Basic Characteristics of Mutations
Mutation Site E28D
Mutation Site Sentence Residues E28, K30, and R18 are highly conserved, with 99.4%, 98.8%, and 99.4% sequence identity across the subtype reference sequences available in the Los Alamos National Laboratory HIV mutation browser (http://hivmut.org [49]). Only three isolates, 03GH173_06 (subtype 06_cpx; GenBank accession number AB286851 [https://www.ncbi.nlm.nih.gov/nuccore/AB286851]), nx2 (subtype 08_BC; GenBank accession number HM067748 [https://www.ncbi.nlm.nih.gov/nuccore/HM067748]), and A32989 (subtype BF1; GenBank accession number AF308491 [https://www.ncbi.nlm.nih.gov/nuccore/AF308491]) show substitutions at those positions with K30R, E28D/K30E, and R18K, respectively (see Table S1 in the supplemental material).
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region Gag
Standardized Encoding Gene Gag  
Genotype/Subtype HIV-1 CRF08_BC
Viral Reference HXB2
Functional Impact and Mechanisms
Disease Cell line    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 30862755
Title Novel Intersubunit Interaction Critical for HIV-1 Core Assembly Defines a Potentially Targetable Inhibitor Binding Pocket
Author Craveur P,Gres AT,Kirby KA,Liu D,Hammond JA,Deng Y,Forli S,Goodsell DS,Williamson JR,Sarafianos SG,Olson AJ
Journal mBio
Journal Info 2019 Mar 12;10(2):e02858-18
Abstract HIV-1 capsid protein (CA) plays critical roles in both early and late stages of the viral replication cycle. Mutagenesis and structural experiments have revealed that capsid core stability significantly affects uncoating and initiation of reverse transcription in host cells. This has led to efforts in developing antivirals targeting CA and its assembly, although none of the currently identified compounds are used in the clinic for treatment of HIV infection. A specific interaction that is primarily present in pentameric interfaces in the HIV-1 capsid core was identified and is reported to be important for CA assembly. This is shown by multidisciplinary characterization of CA site-directed mutants using biochemical analysis of virus-like particle formation, transmission electron microscopy of in vitro assembly, crystallographic studies, and molecular dynamic simulations. The data are consistent with a model where a hydrogen bond between CA residues E28 and K30' from neighboring N-terminal domains (CA(NTD)s) is important for CA pentamer interactions during core assembly. This pentamer-preferred interaction forms part of an N-terminal domain interface (NDI) pocket that is amenable to antiviral targeting.IMPORTANCE Precise assembly and disassembly of the HIV-1 capsid core are key to the success of viral replication. The forces that govern capsid core formation and dissociation involve intricate interactions between pentamers and hexamers formed by HIV-1 CA. We identified one particular interaction between E28 of one CA and K30' of the adjacent CA that appears more frequently in pentamers than in hexamers and that is important for capsid assembly. Targeting the corresponding site could lead to the development of antivirals which disrupt this interaction and affect capsid assembly.
Sequence Data AB286851;HM067748;AF308491
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.