Abstract: We discovered 10 PB2 substitutions that covaried with K627E.
Method: Site-directed mutagenesis was performed using pFLAG-CMV5.1-H7N9-PB2 to generate -K627E, -V139I&K627E, -K191E&K627E, -V511I&K627E, -M535L&K627E, -N559T&K627E, -M570I&K627E, -Q591K&K627E, -I647V&K627E, -
Species difference in ANP32A underlies influenza A virus polymerase host restriction.
Method: Mutations were introduced into the pHW2000-AH1-PB2 plasmid using the QuikChange II Site-Directed Mutagenesis Kit (Stratagene) to generate the K627E, D701N and the double mutations (627E plus 701N).
Identification of potential virulence determinants associated H9N2 avian influenza virus PB2 E627K mutation by comparative proteomics.
Abstract: By iTRAQ method, we found that the mutated K627E contributed to a set of differentially expressed lung proteins, including five upregulated proteins and nine downregulated proteins at 12 h postinfection; ten upregulated proteins and 25 downregulated proteins at 72 h postinfection.
Abstract: Further, three upregulated proteins (moesin, ezrin, and sp-A) caused by PB2 K627E were also confirmed in A549 cells.
Abstract: To investigate the mechanism of increased pathogenicity for H9N2 AIV PB2 627K, we analyzed the difference in mouse lung proteins expression response to PB2 K627E.
Amino acids 473V and 598P of PB1 from an avian-origin influenza A virus contribute to polymerase activity, especially in mammalian cells.
PMID: 22090209
2012
The Journal of general virology
Abstract: In this study, it was found that PB1 from an avian-origin influenza A virus [A/Cambodia/P0322095/2005, H5N1 (Cam)] could enhance the polymerase activity of an attenuated human isolated virus, A/WSN/33, carrying the PB2 K627E mutation (WSN627E) in vitro.
The PB2-E627K mutation attenuates viruses containing the 2009 H1N1 influenza pandemic polymerase.
5Result: A 1918RNP virus in which PB2 residue 627 was ""back-adapted"" to the avian glutamic acid (1918RNP-K627E) consistently grew to a 1- to 2-log-lower peak titer (P = 0.042) than the 1918RNP virus."
Result: Conversely, 1918RNP-K627E virus replication in mouse lung on day 3 was attenuated by more than 1 log compared to the wild-type 1918 RNP-containing virus (7.73 x 105 versus 4.41 x 104 PFU/g; P = 0.019).
Result: Introducing the avian-like PB2-K627E change into the 1918RNP virus rendered the weight loss curve similar to that observed for rNY312.
Result: The 1918RNP-K627E virus, for example, induced almost no inflammatory changes, resembling the findings seen with rNY312.
Table: K627E
A single-amino-acid substitution in a polymerase protein of an H5N1 influenza virus is associated with systemic infection and impaired T-cell activation in mice.
Abstract: A substitution of glutamic acid for lysine at position 627 of the PB2 protein of H5N1 viruses has been identified as a virulence determinant.
Avian Influenza virus glycoproteins restrict virus replication and spread through human airway epithelium at temperatures of the proximal airways.
Method: Mutant viruses were generated in either the A/Victoria/3/75 (H3N2) or A/PR/8/34 (H1N1) genetic background as follows: 1) Vic 627PB2; A/Victoria/3/75 containing a lysine to glutamic acid amino acid substitution at position 627; 2) Vic-226-228HA; A/Victoria/3/75 containing two amino acid substitutions in the HA gene (L226Q, S228G) that confer an avian-like receptor binding preference; 3) Vic+Chick N1; A/Victoria/3/75 in which segment 6 containing the endogenous N2 NA gene was exchanged for the N1 NA gene from avian isolate A/Chick/Italy/1347/99; 4) Vic-226-228HA+Chick N1; A/Victoria/3/75 containing both L226Q and S228G mutations and the avian N1; 5) PR8+Vic HA/
Single mutation at the amino acid position 627 of PB2 that leads to increased virulence of an H5N1 avian influenza virus during adaptation in mice can be compensated by multiple mutations at other sites of PB2.
Abstract: Interestingly, one reverse mutation (K627E) took place at the amino acid position 627 of PB2 during passages of MA5 to MA15, indicating that a lysine at position 627 of PB2 is not absolutely needed for virulence and adaptation in mice by H5N1 virus.
Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E/701N.
Abstract: Introduction of an asparagine at position 701, in conjunction with the K627E mutation, resulted in a phenotype more similar to that of the parental strains, suggesting that this residue can compensate for the lack of 627K in terms of increasing transmission in mammals.
Introduction: Furthermore, the mutation K627E decreases the transmission efficiency of both rPan99 and rVN1203 viruses.
Result: Again, sequencing of the PB2 gene of one transmitted virus indicated that both the K627E and D701N mutations were retained.
Result: Growth in the lungs was affected to a lesser extent by the K627E and D701N mutations than growth in the nasal passages.
IV mutation literature information.
PMID: 
2016
PloS one
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