|
Basic Characteristics of Mutations
|
|
Mutation Site
|
R312A |
|
Mutation Site Sentence
|
Remarkably, no viral RNA was detected in the blood of any of the mice infected with the recEboMA2-VP35/R312A virus at any time point tested (Fig. 2), despite confirmation of infection by the presence of Ebola virus-specific IgG antibodies (data not shown). |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
VP35 |
|
Standardized Encoding Gene
|
VP35
|
|
Genotype/Subtype
|
Zaire |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
Cell line
Hemorrhagic fever, ebola
|
|
Immune
|
Y |
|
Target Gene
|
IRF3
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
18199658
|
|
Title
|
Inhibition of IRF-3 activation by VP35 is critical for the high level of virulence of ebola virus
|
|
Author
|
Hartman AL,Bird BH,Towner JS,Antoniadou ZA,Zaki SR,Nichol ST
|
|
Journal
|
Journal of virology
|
|
Journal Info
|
2008 Mar;82(6):2699-704
|
|
Abstract
|
Zaire ebolavirus causes a rapidly progressing hemorrhagic disease with high mortality. Identification of the viral virulence factors that contribute to the severity of disease induced by Ebola virus is critical for the design of therapeutics and vaccines against the disease. Given the rapidity of disease progression, virus interaction with the innate immune system early in the course of infection likely plays an important role in determining the outcome of the disease. The Ebola virus VP35 protein inhibits the activation of IRF-3, a critical transcription factor for the induction of early antiviral immunity. Previous studies revealed that a single amino acid change (R312A) in VP35 renders the protein unable to inhibit IRF-3 activation. A reverse-genetics-generated, mouse-adapted, recombinant Ebola virus that encodes the R312A mutation in VP35 was produced. We found that relative to the case for wild-type virus containing the authentic VP35 sequence, this single amino acid change in VP35 renders the virus completely attenuated in mice. Given that these viruses differ by only a single amino acid in the IRF-3 inhibitory domain of VP35, the level of alteration of virulence is remarkable and highlights the importance of VP35 for the pathogenesis of Ebola virus.
|
|
Sequence Data
|
-
|