|
Basic Characteristics of Mutations
|
|
Mutation Site
|
T148K |
|
Mutation Site Sentence
|
The T148K substitution in NA has been found in recent H3N2 influenza A isolates and influenza B isolates. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
NA |
|
Standardized Encoding Gene
|
NA
|
|
Genotype/Subtype
|
H3N2 |
|
Viral Reference
|
KJ609203—KJ609210
|
|
Functional Impact and Mechanisms
|
|
Disease
|
-
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
America |
|
Literature Information
|
|
PMID
|
27351973
|
|
Title
|
Two Escape Mechanisms of Influenza A Virus to a Broadly Neutralizing Stalk-Binding Antibody
|
|
Author
|
Chai N,Swem LR,Reichelt M,Chen-Harris H,Luis E,Park S,Fouts A,Lupardus P,Wu TD,Li O,McBride J,Lawrence M,Xu M,Tan MW
|
|
Journal
|
PLoS pathogens
|
|
Journal Info
|
2016 Jun 28;12(6):e1005702
|
|
Abstract
|
Broadly neutralizing antibodies targeting the stalk region of influenza A virus (IAV) hemagglutinin (HA) are effective in blocking virus infection both in vitro and in vivo. The highly conserved epitopes recognized by these antibodies are critical for the membrane fusion function of HA and therefore less likely to be permissive for virus mutational escape. Here we report three resistant viruses of the A/Perth/16/2009 strain that were selected in the presence of a broadly neutralizing stalk-binding antibody. The three resistant viruses harbor three different mutations in the HA stalk: (1) Gln387Lys; (2) Asp391Tyr; (3) Asp391Gly. The Gln387Lys mutation completely abolishes binding of the antibody to the HA stalk epitope. The other two mutations, Asp391Tyr and Asp391Gly, do not affect antibody binding at neutral pH and only slightly reduce binding at low pH. Interestingly, they enhance the fusion ability of the HA, representing a novel mechanism that allows productive membrane fusion even in the presence of antibody and hence virus escape from antibody neutralization. Therefore, these mutations illustrate two different resistance mechanisms used by IAV to escape broadly neutralizing stalk-binding antibodies. Compared to the wild type virus, the resistant viruses release fewer progeny viral particles during replication and are more sensitive to Tamiflu, suggesting reduced viral fitness.
|
|
Sequence Data
|
-
|
|
|