HIV Mutation Detail Information

Virus Mutation HIV Mutation S640H


Basic Characteristics of Mutations
Mutation Site S640H
Mutation Site Sentence Several features in the sequence of F8 Env could explain this result, such as the lack of the N295 glycan at the base of V3, a K-to-E substitution at position 490 in the C5 region of gp120, and several mutations within the HR2 region of gp41 (S640H and L and N residues at positions 641 and 644) (S3D Fig).
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region Env
Standardized Encoding Gene Env  
Genotype/Subtype HIV-1
Viral Reference HxB2
Functional Impact and Mechanisms
Disease HIV Infections    
Immune Y
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location Amsterdam
Literature Information
PMID 33872329
Title Mechanisms of HIV-1 evasion to the antiviral activity of chemokine CXCL12 indicate potential links with pathogenesis
Author Armani-Tourret M,Zhou Z,Gasser R,Staropoli I,Cantaloube-Ferrieu V,Benureau Y,Garcia-Perez J,Perez-Olmeda M,Lorin V,Puissant-Lubrano B,Assoumou L,Delaugerre C,Lelievre JD,Levy Y,Mouquet H,Martin-Blondel G,Alcami J,Arenzana-Seisdedos F,Izopet J,Colin P,Lagane B
Journal PLoS pathogens
Journal Info 2021 Apr 19;17(4):e1009526
Abstract HIV-1 infects CD4 T lymphocytes (CD4TL) through binding the chemokine receptors CCR5 or CXCR4. CXCR4-using viruses are considered more pathogenic, linked to accelerated depletion of CD4TL and progression to AIDS. However, counterexamples to this paradigm are common, suggesting heterogeneity in the virulence of CXCR4-using viruses. Here, we investigated the role of the CXCR4 chemokine CXCL12 as a driving force behind virus virulence. In vitro, CXCL12 prevents HIV-1 from binding CXCR4 and entering CD4TL, but its role in HIV-1 transmission and propagation remains speculative. Through analysis of thirty envelope glycoproteins (Envs) from patients at different stages of infection, mostly treatment-naive, we first interrogated whether sensitivity of viruses to inhibition by CXCL12 varies over time in infection. Results show that Envs resistant (RES) to CXCL12 are frequent in patients experiencing low CD4TL levels, most often late in infection, only rarely at the time of primary infection. Sensitivity assays to soluble CD4 or broadly neutralizing antibodies further showed that RES Envs adopt a more closed conformation with distinct antigenicity, compared to CXCL12-sensitive (SENS) Envs. At the level of the host cell, our results suggest that resistance is not due to improved fusion or binding to CD4, but owes to viruses using particular CXCR4 molecules weakly accessible to CXCL12. We finally asked whether the low CD4TL levels in patients are related to increased pathogenicity of RES viruses. Resistance actually provides viruses with an enhanced capacity to enter naive CD4TL when surrounded by CXCL12, which mirrors their situation in lymphoid organs, and to deplete bystander activated effector memory cells. Therefore, RES viruses seem more likely to deregulate CD4TL homeostasis. This work improves our understanding of the pathophysiology and the transmission of HIV-1 and suggests that RES viruses' receptors could represent new therapeutic targets to help prevent CD4TL depletion in HIV+ patients on cART.
Sequence Data MT951984;MT951985;MT951986;MT951987;MT951988;MT951989;MT951990;MT951991;MT951992;MT951993;MT951994;MT951995
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.