EBOV Mutation Detail Information

Virus Mutation EBOV Mutation T603D


Basic Characteristics of Mutations
Mutation Site T603D
Mutation Site Sentence NPwt with either T603I or T603D showed no significant effect on VP30 phosphorylation (Figure 4F).
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region NP
Standardized Encoding Gene NP
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease Cell line    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 39726359
Title To be or not to be phosphorylated: understanding the role of Ebola virus nucleoprotein in the dynamic interplay with the transcriptional activator VP30 and the host phosphatase PP2A-B56
Author Kamper L,Kuhl I,Vallbracht M,Hoenen T,Linne U,Weber A,Chlanda P,Kracht M,Biedenkopf N
Journal Emerging microbes & infections
Journal Info 2025 Dec;14(1):2447612
Abstract Ebola virus (EBOV) transcription is essentially regulated via dynamic dephosphorylation of its viral transcription activator VP30 by the host phosphatase PP2A. The nucleoprotein NP has emerged as a third key player in the regulation of this process by recruiting both the regulatory subunit B56 of PP2A and its substrate VP30 to initiate VP30 dephosphorylation and hence viral transcription. Both binding sites are located in close proximity to each other in NP's C-terminal-disordered region. This study investigates NP's role in VP30 dephosphorylation and transcription activation, focussing on the spatial requirements of NP's binding sites. Increasing the distance between PP2A-B56 and VP30 at the NP interface revealed that close spatial and orientational contact is necessary for efficient VP30 dephosphorylation and viral transcription. Longer distances were lethal for recombinant EBOV except when a compensatory mutation, NP-T603I, occurred. This mutation, located between the NP binding sites for PP2A-B56 and VP30, fully restored functionality. Mass spectrometry showed that T603 is phosphorylated in recEBOV-NPwt virions. Mutational analysis indicated that T603I facilitates VP30 dephosphorylation in otherwise lethal recEBOV and that dynamic phosphorylation of NP-T603 is important for efficient primary viral transcription in the WT context. These findings emphasize the critical and evolutionarily pressured interplay between VP30 and PP2A-B56 within the NP C-terminal-disordered region and highlight the important role of NP on the regulation of viral transcription during the EBOV life cycle.
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.