HIV Mutation Detail Information

Virus Mutation HIV Mutation F195A


Basic Characteristics of Mutations
Mutation Site F195A
Mutation Site Sentence To gain insight into the molecular mechanism by which NEF impairs CD4 T‐cell help, we analyzed the activity of a series of mutant NEF proteins in the adoptive transfer model (Fig 3A). This included NEF F195A which lacks the ability to associate with the cellular p21‐activated kinase 2 (PAK2) to negatively modulate host cell actin dynamics and motility (O'Neill et al, 2006; Stolp et al, 2009; Stolp et al, 2012), a NEF variant with disrupted di‐leucine motif (NEF LLAA) that lacks the ability to internalize cell surface receptors such as CD4 (Craig et al, 1998; Greenberg et al, 1998), NEF AxxA in which an SH3 domain‐binding PxxP motif is disrupted and fails, e.g., to relocalize the TCR proximal kinase Lck from the plasma membrane to intracellular compartments (Saksela et al, 1995; Pan et al, 2012), as well as NEF variants carrying a deletion of an N‐terminal protein interaction platform (NEF ∆12‐39) or a mutation in an interaction motif within residues 12‐39 (NEF A32‐39) required for CD4 downregulation and SERINC5 antagonism (Ananth et al, 2019).
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 HIV Infections    
Immune Y
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 33146906
Title HIV-1 infection of CD4 T cells impairs antigen-specific B cell function
Author Kaw S,Ananth S,Tsopoulidis N,Morath K,Coban BM,Hohenberger R,Bulut OC,Klein F,Stolp B,Fackler OT
Journal The EMBO journal
Journal Info 2020 Dec 15;39(24):e105594
Abstract Failures to produce neutralizing antibodies upon HIV-1 infection result in part from B-cell dysfunction due to unspecific B-cell activation. How HIV-1 affects antigen-specific B-cell functions remains elusive. Using an adoptive transfer mouse model and ex vivo HIV infection of human tonsil tissue, we found that expression of the HIV-1 pathogenesis factor NEF in CD4 T cells undermines their helper function and impairs cognate B-cell functions including mounting of efficient specific IgG responses. NEF interfered with T cell help via a specific protein interaction motif that prevents polarized cytokine secretion at the T-cell-B-cell immune synapse. This interference reduced B-cell activation and proliferation and thus disrupted germinal center formation and affinity maturation. These results identify NEF as a key component for HIV-mediated dysfunction of antigen-specific B cells. Therapeutic targeting of the identified molecular surface in NEF will facilitate host control of HIV infection.
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.