ZIKV Mutation Detail Information

Virus Mutation ZIKV Mutation N154A


Basic Characteristics of Mutations
Mutation Site N154A
Mutation Site Sentence Instead, genetic engineering has been used to generate mutant viruses that, for instance, contain a N154A substitution.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region E
Standardized Encoding Gene envelope
Genotype/Subtype -
Viral Reference KU527068
Functional Impact and Mechanisms
Disease Cell line    
Immune -
Target Gene TRAPPC1    NUPR1    ATF4   
Clinical and Epidemiological Correlations
Clinical Information -
Treatment Tunicamycin
Location -
Literature Information
PMID 40291117
Title Evolution of Zika virus in Rag1-deficient mice selects for unique envelope glycosylation motif mutants that show enhanced replication fitness
Author Nakayama E,Tang B,Stewart R,Cox AL,Yan K,Bishop CR,Dumenil T,Nguyen W,Slonchak A,Sng J,Khromykh AA,Lutzky VP,Rawle DJ,Suhrbier A
Journal Virus evolution
Journal Info 2025 Apr 11;11(1):veaf021
Abstract N-linked glycosylation of flavivirus envelope proteins is widely viewed as being required for optimal folding, processing and/or transit of envelope proteins, and the assembling virons, through the endoplasmic reticulum (ER) and the Golgi. Zika virus (ZIKV) has a single N-linked envelope glycan located adjacent to the fusion loop. Herein we show that independent serial passage of ZIKV(Natal) in Rag1 (-/-) mice for 223 or 386 days generated two unique envelope glycan-deficient mutants, ZIKV-V153D and ZIKV-N154D, respectively. Surprisingly, these mutants grew to titres approximately 1 to 2.6 logs higher than the glycosylated parental ZIKV(Natal) in Vero E6 cells and human brain organoids. RNA-Seq of infected organoids suggested that this increased replication fitness was associated with upregulation of the unfolded protein response (UPR). Cell death, cellular viral RNA, and viral protein levels were not significantly affected, arguing that these glycan mutants enjoyed faster ER/Golgi folding, processing, assembly, transit, and virion egress, assisted by an upregulated UPR. Thus, ZIKV envelope N-linked glycosylation is not essential for promoting envelope folding, assembly, and transit through the ER/Golgi, since aspartic acid (D) substitutions in the glycosylation motif can achieve this with significantly greater efficiency. Instead, the evolution of glycan mutants in Rag1 (-/-) mice indicates that such envelope glycosylation can have a fitness cost in an environment devoid of virus-specific antibody responses. The V153D and N154D mutations, generated by natural selection in Rag1 (-/-) mice, have to date not been employed in orthoflavivirus envelope glycosylation studies. Instead, genetic engineering has been used to generate mutant viruses that, for instance, contain a N154A substitution. The latter may impart confounding unfavourable properties, such as envelope protein insolubility, that have a detrimental impact on virus replication. The V153D and N154D substitutions may avoid imparting unfavourable properties by preserving the surface negative charge provided by the glycan moiety in the parental ZIKV(Natal) envelope protein. In Ifnar1 (-/-) mice ZIKV-V153D and -N154D showed faster viremia onsets, but reduced viremic periods, than the parental ZIKV(Natal), consistent with an established contention that such glycans have evolved to delay neutralizing antibody activity.
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.