|
Basic Characteristics of Mutations
|
|
Mutation Site
|
M101I |
|
Mutation Site Sentence
|
The M101I mutation of H5N1 NS1, namely H5-M101I, fully reversed its functions. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
NS1 |
|
Standardized Encoding Gene
|
NS
|
|
Genotype/Subtype
|
H5N1 |
|
Viral Reference
|
A/PR/8/34 wild type
|
|
Functional Impact and Mechanisms
|
|
Disease
|
Influenza A
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
Puerto Rico |
|
Literature Information
|
|
PMID
|
23124793
|
|
Title
|
Methionine-101 from one strain of H5N1 NS1 protein determines its IFN-antagonizing ability and subcellular distribution pattern
|
|
Author
|
Meng J,Zhang Z,Zheng Z,Liu Y,Wang H
|
|
Journal
|
Science China. Life sciences
|
|
Journal Info
|
2012 Nov;55(11):933-9
|
|
Abstract
|
Influenza A virus NS1 protein has developed two main IFN-antagonizing mechanisms by inhibiting retinoic-acid-inducible gene I (RIG-I) signal transduction, or by suppressing cellular pre-mRNA processing through binding to cleavage and polyadenylation specific factor 30 (CPSF30). However, the precise effects of NS1 on suppressing type I IFN induction have not been well characterized. Here we report that compared with PR/8/34 NS1, which is localized partially in the cytoplasm and has strong IFN-antagonizing ability via specifically inhibiting IFN-beta promoter activity, H5N1 NS1 has strikingly different characteristics. It mainly accumulates in the nucleus of transfected cells and exerts rather weak IFN-counteracting ability through suppression of the overall gene expression. The M101I mutation of H5N1 NS1, namely H5-M101I, fully reversed its functions. H5-M101I gained the ability to specifically inhibit IFN-beta promoter activity, translocate to the cytoplasm, and release CPSF30. The previously reported NES (nuclear export signal) (residues 138-147) was unable to lead H5N1 NS1 to translocate. This suggests that other residues may serve as a potent NES. Findings indicated that together with leucine-100, methionine-101 enhanced the regional NES. In addition, methionine-101 was the key residue for the NS1-CPSF30 interaction. This study reveals the importance of methionine-101 in the influenza A virus life cycle and may provide valuable information for antiviral strategies.
|
|
Sequence Data
|
-
|