JEV Mutation Detail Information

Virus Mutation JEV Mutation K166R


Basic Characteristics of Mutations
Mutation Site K166R
Mutation Site Sentence Furthermore, double mutations of K136R-K166R attenuated JEV infection in vitro and reduced viral virulence in mice.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region E
Standardized Encoding Gene envelope
Genotype/Subtype -
Viral Reference OP588746
Functional Impact and Mechanisms
Disease Cell line    
Immune -
Target Gene IFNB1   
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 40071916
Title E3 ubiquitin ligase MARCH5 positively regulates Japanese encephalitis virus infection by catalyzing the K27-linked polyubiquitination of viral E protein and inhibiting MAVS-mediated type I interferon production
Author Li C,Tang C,Liu X,Liu Y,Zhang L,Shi J,Li Q,Sun M,Li Y
Journal mBio
Journal Info 2025 Apr 9;16(4):e0020825
Abstract Membrane-associated RING-CH-type finger (MARCH) proteins, a class of E3 ubiquitin ligases, have been reported to be involved in the infection of multiple viruses and the regulation of type I interferon (IFN) production. However, the specific role and mechanisms by which MARCH proteins influence Japanese encephalitis virus (JEV) infection remain poorly understood. Here, we systematically investigate the functional relevance of MARCH proteins in JEV replication by examining the effects of siRNA-mediated knockdown of MARCHs on viral infection. We identified MARCH5 as a positive regulator of JEV replication. The knockout of MARCH5 dramatically reduced viral yields, whereas its overexpression significantly enhanced JEV replication. Mechanistically, MARCH5 specifically interacts with the JEV envelope (E) protein and promotes its K27-linked polyubiquitination at the lysine (K) residues 136 and 166. This ubiquitination enhances viral attachment to permissive cells. Substituting these lysine residues with arginine (R) attenuated JEV replication in vitro and reduced viral virulence in vivo. Furthermore, JEV infection upregulated the expression of MARCH5. We also discovered that MARCH5 degrades mitochondrial antiviral-signaling protein (MAVS) through the ubiquitin-proteasome pathway by catalyzing its K48-linked ubiquitination, thereby inhibiting type I IFN production in JEV-infected cells. This suppression of type I IFN further facilitates JEV infection. In conclusion, these findings disclosed a novel role of MARCH5 in positively regulating JEV infection and revealed an important mechanism employed by MARCH5 to regulate the innate immune response.IMPORTANCEJEV is the leading cause of viral encephalitis in many countries of Asia with an estimated 100,000 clinical human cases and causes economic loss to the swine industry. Until now, there is no clinically approved antiviral for the treatment of JEV infection. Although vaccination prophylaxis is widely regarded as the most effective strategy for preventing Japanese encephalitis (JE), the incidence of JE cases continues to rise. Thus, a deeper understanding of virus-host interaction will enrich our knowledge of the mechanisms underlying JEV infection and identify novel targets for the development of next-generation live-attenuated vaccines and antiviral therapies. To the best of our knowledge, this study is the first to identify MARCH5 as a pro-viral host factor that facilitates JEV infection. We elucidated two distinct mechanisms by which MARCH5 promotes JEV infection. First, MARCH5 interacts with viral E protein and mediates the K27-linked ubiquitination of E protein at the K136 and K166 residues to facilitate efficient viral attachment. Furthermore, double mutations of K136R-K166R attenuated JEV infection in vitro and reduced viral virulence in mice. Second, the upregulated expression of MARCH5 induced by JEV infection further suppresses the RIG-I-like receptor (RLR) signaling pathway to benefit viral infection. MARCH5 downregulates type I IFN production by conjugating the K48-linked polyubiquitin at the K286 of MAVS, which leads to MAVS degradation through the ubiquitin-proteasome pathway. In summary, this study provides novel insights into the role played by MARCH proteins in JEV infection and identifies specific ubiquitination sites on JEV E protein that could be targeted for viral attenuation and the development of antiviral therapeutics.
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.