Double mutations in the H9N2 avian influenza virus PB2 gene act cooperatively to increase viral host adaptation and replication for human infections.
PMID: 34061017
2021
The Journal of general virology
Abstract: K526R, E627V or E627K), indicating a host adaptation advantage for these double mutations.
Deep sequencing of the transcriptome from murine lung infected with H5N8 subtype avian influenza virus with combined substitutions I283M and K526R in PB2 gene.
PMID: 33309772
2021
Infection, genetics and evolution
Abstract: Especially, PB2-I283M-K526R mutation strongly induced a sharp expression of cytokine storm-related genes, including MX1, CXCL10, and IFN-gamma, performed by qRT-PCR.
Abstract: Here, RNA-seq method was used to analyze the global host response of murine lungs after infecting with parental r-JY virus and JY-PB2-I283M-K526R mutant virus.
Abstract: Taken together, our data demonstrated that PB2-I283M-K526R of H5N8 subtype HPAIV exacerbated the innate immune response and the level of cell apoptosis, which might be a key pathogenic mechanism for the enhanced pathogenicity of mutants in mammals.
Abstract: We also found that P
PA Mutations Inherited during Viral Evolution Act Cooperatively To Increase Replication of Contemporary H5N1 Influenza Virus with an Expanded Host Range.
Introduction: In addition, we recently reported that the H9N2 virus in the Middle East (G1-A/B subclade), centered in Egypt, commonly carries the PB2-E627V, -E543D, -A655V, and -K526R mutations, which all contributed to more fit replication in human cells and mice.
Introduction: Other mammal adaptation mutations include PB2-D701N, -K526R, -Q591K, -E192K, -K702R, and -E627V.
Introduction: These results contrasted those for viruses isolated in Asia, where representative human adaptation mutations (e.g., PB2-
Dynamic PB2-E627K substitution of influenza H7N9 virus indicates the in vivo genetic tuning and rapid host adaptation.
Discussion: PB2-K526R has been shown to interact with nuclear export protein, which enhances virus replication, particularly in combination with 627K.
Discussion: Furthermore, PB2-K526R is found in human isolates of H7N9 (84%), H5N1 (74%), and H3N2 (99.7%).
Discussion: In contrast, K526R/E627K multiple mutations occurred in the field and had strong orchestral effects on mammalian adaptation of H7N9 and H9N2 viruses.
Discussion: Previous studies have implied distinct roles of D701N and K526R when combined with E627K.
Discussion: showed that PB2-E627
Enhanced Potency of a Broad H7N9-Neutralizing Antibody HNIgGA6 Through Structure-Based Design.
Introduction: H7N9 has also acquired some other mammalian-adapted genetic changes, including T271A, K526R, A588V, E627K, or D701N in the viral PB2, which facilitated viral replication and increased viral-induced disease severity in mammals.
Effect of the selection pressure of vaccine antibodies on evolution of H9N2 avian influenza virus in chickens.
Result: In the 20 strains isolated from the tracheas of chickens with selection pressure, PB2 of 1 strain (5%) had a D256N mutation, PB2 of 13 strains (65%) had an R318K mutation and PB2 of 20 strain (100%) had an R355K mutation; in the 24 strains isolated from the tracheas of chickens with selection pressure, PB2 of 19 strains (79.1%) had an R318K mutation, PB2 of 24 strains (100%) had an R355K mutation PB2 of 1 strain (5.2%) had a K526R mutation, and PB2 of 2 strains (10.5%) had an A622V mutation.|mgd
Evolved avian influenza virus (H7N9) isolated from human cases in a middle Yangtze River city in China, from February to April 2017.
Result: In changsha city, PB2 Ala588Val mutation site was presented in five of the isolates and K526R mutation site was presented in one of the isolates in this wave.
Prevailing I292V PB2 mutation in avian influenza H9N2 virus increases viral polymerase function and attenuates IFN-beta induction in human cells.
PMID: 31305236
2019
The Journal of general virology
Introduction: To overcome this restriction, the avian PB2 gene needs to acquire certain mutational changes to improve its activity in mammalian cells, as exemplified in PB2-E627K, -D701N, -T271A, -K526R and -A588V.
The PB2 Polymerase Host Adaptation Substitutions Prime Avian Indonesia Sub Clade 2.1 H5N1 Viruses for Infecting Humans.
Abstract: Testing the hypothesis that this mutation may prime avian H5N1 virus for human infection, we showed that: (1) K526R is rarely found in avian influenza viruses but was identified in H5N1 viruses 2-3 years after the virus emerged in Indonesia, coincident with the emergence of H5N1 human infections in Indonesia; (2) K526R is required for efficient replication of Indonesia H5N1 virus in mammalian cells in vitro and in vivo and reverse substitution to 526K in human isolates abolishes this ability; (3) Indonesian H5N1 virus, which contains K526R-PB2, is stable and does not further acquire E627K following replication in infected mice; and (4) virus containing K526R-PB2 shows no fitness d
Multiple amino acid substitutions involved in the adaption of three avian-origin H7N9 influenza viruses in mice.
Discussion: In addition to the most often-observed substitution of E627K, there are several other important mutations in the PB2 protein, such as E158G, D253N, T271A, K526R, Q591K, A588V, D701N and so on, and these mutations had been proved to enhance polymerase activity.
IV mutation literature information.
PMID: 
2021
The Journal of general virology
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