EBOV Mutation Detail Information

Virus Mutation EBOV Mutation E619K


Basic Characteristics of Mutations
Mutation Site E619K
Mutation Site Sentence The NP E619K mutation moderately reduced the EBOV minigenome transcription, which was restored by the treatment with 1E7-03.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region NP
Standardized Encoding Gene NP
Genotype/Subtype -
Viral Reference NC_002549.1
Functional Impact and Mechanisms
Disease Cell line    
Immune -
Target Gene EIF2S1    SIRT1    RAN    PPA1   
Clinical and Epidemiological Correlations
Clinical Information -
Treatment 1E7-03
Location -
Literature Information
PMID 40288648
Title Ebola virus nucleoprotein interaction with host protein phosphatase-1 regulates its dimerization and capsid formation
Author Ahmad A,Tigabu B,Ivanov A,Jerebtsova M,Ammosova T,Ramanathan P,Kumari N,Brantner CA,Pietzsch CA,Simhadri J,Abdullah G,Uversky VN,Paromov V,Popratiloff A,Widen S,Bukreyev A,Nekhai S
Journal The Journal of biological chemistry
Journal Info 2025 Jun;301(6):108541
Abstract Ebola virus (EBOV) replication is regulated by the host protein phosphatases, PP1 and PP2A, which dephosphorylate the transcriptional cofactor of EBOV polymerase VP30. The PP1-targeting compound 1E7-03 induces VP30 phosphorylation and inhibits EBOV infection. Here, we investigate the broader role of PP1 in EBOV replication and transcription, including its interaction with nucleoprotein (NP). When EBOV-infected cells were continuously treated with 1E7-03, the NP E619K mutation was found and selected for further analysis. The NP E619K mutation moderately reduced the EBOV minigenome transcription, which was restored by the treatment with 1E7-03. Proteomics, immunoprecipitation, dimerization, split NanoBit, and colocalization analyses indicated that NP interacts with PP1 and that NP E619K mutations enhanced this binding. Treatment with 1E7-03 dissociated PP1-NP complex, but enhanced NP dimerization, which was more pronounced for NP E619K mutant. Mutation and deletion analyses pointed to several potential PP1-binding sites in NP that were located in the moderately disordered NP regions. When NP was co-expressed with VP24 and VP35, formation of EBOV capsids was impaired with NP E619K mutation. Treatment with 1E7-03 restored the capsid formation by the NP E619K mutant but inhibited capsids formed by WT NP. Our findings suggest that PP1 binds to NP and that this binding might regulate NP dimerization and capsid formation. Collectively, our results point to a new role for PP1 in EBOV replication, in which NP binding to PP1 may facilitate viral transcription by delaying capsid formation and EBOV replication.
Sequence Data 1-20240823-063919-3403965
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.