HIV Mutation Detail Information

Virus Mutation HIV Mutation L184F


Basic Characteristics of Mutations
Mutation Site L184F
Mutation Site Sentence The L184F mutation altered the trimer conformation by modulating intramolecular interactions stabilizing the trimer apex and led to viral escape from autologous plasma bnAbs and known N160 glycan-targeted bnAbs.
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 -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment Env
Location India
Literature Information
PMID 32669335
Title A Rare Mutation in an Infant-Derived HIV-1 Envelope Glycoprotein Alters Interprotomer Stability and Susceptibility to Broadly Neutralizing Antibodies Targeting the Trimer Apex
Author Mishra N,Sharma S,Dobhal A,Kumar S,Chawla H,Singh R,Das BK,Kabra SK,Lodha R,Luthra K
Journal Journal of virology
Journal Info 2020 Sep 15;94(19):e00814-20
Abstract The envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) is the sole target of broadly neutralizing antibodies (bnAbs). Several mechanisms, such as the acquisition of mutations, variability of the loop length, and alterations in the glycan pattern, are employed by the virus to shield neutralizing epitopes on Env to sustain survival and infectivity within the host. The identification of mutations that lead to viral evasion of the host immune response is essential for the optimization and engineering of Env-based trimeric immunogens. Here, we report a rare leucine-to-phenylalanine escape mutation (L184F) at the base of hypervariable loop 2 (population frequency of 0.0045%) in a 9-month-old perinatally HIV-1-infected infant broad neutralizer. The L184F mutation altered the trimer conformation by modulating intramolecular interactions stabilizing the trimer apex and led to viral escape from autologous plasma bnAbs and known N160 glycan-targeted bnAbs. The L184F amino acid change led to the acquisition of a relatively open trimeric conformation, often associated with tier 1 HIV-1 isolates and increased susceptibility to neutralization by polyclonal plasma antibodies of weak neutralizers. While there was no impact of the L184F mutation on free virus transmission, a reduction in cell-to-cell transmission was observed. In conclusion, we report a naturally selected viral mutation, L184F, that influenced a change in the conformation of the Env trimer apex as a mechanism of escape from contemporaneous plasma V2 apex-targeted nAbs. Further studies should be undertaken to define viral mutations acquired during natural infection, to escape selection pressure exerted by bnAbs, to inform vaccine design and bnAb-based therapeutic strategies.IMPORTANCE The design of HIV-1 envelope-based immunogens capable of eliciting broadly neutralizing antibodies (bnAbs) is currently under active research. Some of the most potent bnAbs target the quaternary epitope at the V2 apex of the HIV-1 Env trimer. By studying naturally circulating viruses from a perinatally HIV-1-infected infant with plasma neutralizing antibodies targeted to the V2 apex, we identified a rare leucine-to-phenylalanine substitution, in two out of six functional viral clones, that destabilized the trimer apex. This single-amino-acid alteration impaired the interprotomeric interactions that stabilize the trimer apex, resulting in an open trimer conformation and escape from broadly neutralizing autologous plasma antibodies and known V2 apex-directed bnAbs, thereby favoring viral evasion of the early bnAb response of the infected host. Defining the mechanisms by which naturally occurring viral mutations influence the sensitivity of HIV-1 to bnAbs will provide information for the development of vaccines and bnAbs as anti-HIV-1 reagents.
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.