HIV Mutation Detail Information

Virus Mutation HIV Mutation G2A


Basic Characteristics of Mutations
Mutation Site G2A
Mutation Site Sentence To determine the impact of Nef myristoylation on the formation of iProteasomes, the second amino acid of Nef glycine, which is critical for the myristoylation of Nef (36), was mutated to alanine (Nef-G2A).
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region Nef
Standardized Encoding Gene Nef  
Genotype/Subtype HIV-1
Viral Reference -
Functional Impact and Mechanisms
Disease Acquired Immunodeficiency Syndrome    
Immune Y
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment Nef
Location -
Literature Information
PMID 33109760
Title HIV-1 Nef Interacts with LMP7 To Attenuate Immunoproteasome Formation and Major Histocompatibility Complex Class I Antigen Presentation
Author Yang Y,Liu W,Hu D,Su R,Ji M,Huang Y,Shereen MA,Xu X,Luo Z,Zhang Q,Liu F,Wu K,Liu Y,Wu J
Journal mBio
Journal Info 2020 Oct 27;11(5):e02221-19
Abstract The proteasome is a major protein degradation machinery with essential and diverse biological functions. Upon induction by cytokines, proteasome subunits beta1, beta2, and beta5 are replaced by beta1i/LMP2, beta2i/MECL-1, and beta5i/LMP7, resulting in the formation of an immunoproteasome (iProteasome). iProteasome-degraded products are loaded onto the major histocompatibility complex class I (MHC-I), regulating immune responses and inducing cytotoxic T lymphocytes (CTLs). Human immunodeficiency virus type 1 (HIV-1) is the causal agent of AIDS. HIV-1-specific CTLs represent a critical immune mechanism limiting viral replication. HIV-1 negative regulatory factor (Nef) counteracts host immunity, particularly the response involving MHC-I/CTL. This study identifies a distinct mechanism by which Nef facilitates immune evasion via suppressing the function of iProteasome and MHC-I. Nef interacts with LMP7 on the endoplasmic reticulum (ER), downregulating the incorporation of LMP7 into iProteasome and thereby attenuating its formation. Moreover, Nef represses the iProteasome function of protein degradation, MHC-I trafficking, and antigen presentation.IMPORTANCE The ubiquitin-proteasome system (UPS) is essential for the degradation of damaged proteins, which takes place in the proteasome. Upon activation by cytokines, the catalytic subunits of the proteasome are replaced by distinct isoforms resulting in the formation of an immunoproteasome (iProteasome). iProteasome generates peptides used by major histocompatibility complex class I (MHC-I) for antigen presentation and is essential for immune responses. HIV-1 is the causative agent of AIDS, and HIV-1-specific cytotoxic T lymphocytes (CTLs) provide immune responses limiting viral replication. This study identifies a distinct mechanism by which HIV-1 promotes immune evasion. The viral protein negative regulatory factor (Nef) interacts with a component of iProteasome, LMP7, attenuating iProteasome formation and protein degradation function, and thus repressing the MHC-I antigen presentation activity of MHC-I. Therefore, HIV-1 targets LMP7 to inhibit iProteasome activation, and LMP7 may be used as the target for the development of anti-HIV-1/AIDS 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.