|
Basic Characteristics of Mutations
|
|
Mutation Site
|
E627K |
|
Mutation Site Sentence
|
Mutations E627K and D701N in the PB2 protein have previously been identified as determinants of avian and pandemic influenza virus virulence in mammals. |
|
Mutation Level
|
Amino acid level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
PB2 |
|
Standardized Encoding Gene
|
PB2
|
|
Genotype/Subtype
|
H1N1 |
|
Viral Reference
|
A/Netherlands/602/2009 wild type
|
|
Functional Impact and Mechanisms
|
|
Disease
|
Influenza A
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
- |
|
Treatment
|
- |
|
Location
|
Netherlands |
|
Literature Information
|
|
PMID
|
20130063
|
|
Title
|
Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission
|
|
Author
|
Herfst S,Chutinimitkul S,Ye J,de Wit E,Munster VJ,Schrauwen EJ,Bestebroer TM,Jonges M,Meijer A,Koopmans M,Rimmelzwaan GF,Osterhaus AD,Perez DR,Fouchier RA
|
|
Journal
|
Journal of virology
|
|
Journal Info
|
2010 Apr;84(8):3752-8
|
|
Abstract
|
In the first 6 months of the H1N1 swine-origin influenza virus (S-OIV) pandemic, the vast majority of infections were relatively mild. It has been postulated that mutations in the viral genome could result in more virulent viruses, leading to a more severe pandemic. Mutations E627K and D701N in the PB2 protein have previously been identified as determinants of avian and pandemic influenza virus virulence in mammals. These mutations were absent in S-OIVs detected early in the 2009 pandemic. Here, using reverse genetics, mutations E627K, D701N, and E677G were introduced into the prototype S-OIV A/Netherlands/602/2009, and their effects on virus replication, virulence, and transmission were investigated. Mutations E627K and D701N caused increased reporter gene expression driven by the S-OIV polymerase complex. None of the three mutations affected virus replication in vitro. The mutations had no major impact on virus replication in the respiratory tracts of mice and ferrets or on pathogenesis. All three mutant viruses were transmitted via aerosols or respiratory droplets in ferrets. Thus, the impact of key known virulence markers in PB2 in the context of current S-OIVs was surprisingly small. This study does not exclude the possibility of emergence of S-OIVs with other virulence-associated mutations in the future. We conclude that surveillance studies aimed at detecting S-OIVs with increased virulence or transmission should not rely solely on virulence markers identified in the past but should include detailed characterization of virus phenotypes, guided by genetic signatures of viruses detected in severe cases of disease in humans.
|
|
Sequence Data
|
-
|
|
|