Introduction: The majority of the mammalian adaptive substitutions occur in the PB2 protein; E627K and D710N are two well-characterized substitutions in PB2 protein, which are critical for mammalian adaptation in multiple subtypes of avian influenza viruses.
Continuing evolution of H6N2 influenza a virus in South African chickens and the implications for diagnosis and control.
Introduction: Hence, identifying a common denominator for the enhanced pathogenicity of IBVs, such as the E627K PB2 mutation of avian IAVs, may be of great importance because such defined IBV pathogenic determinants might be useful for the interpretation of IBV virulence and host range.
Introduction: The PB2 E627K mutation of avian IAVs has been suggested to be associated with pathogenicity in mice.
Amino Acid Substitutions HA A150V, PA A343T, and PB2 E627K Increase the Virulence of H5N6 Influenza Virus in Mice.
Abstract: However, HA A150V and PA A343T seemed to attenuate PB2 E627K in vivo, which implies the difference between mixed viral populations under natural condition and single population under experiment, specialization and cooperation in quasispecies is important in the process of adaption.
Abstract: In addition, we show that PA A343T dramatically exacerbates the effect of PB2 E627K on viral polymerase activity; when combined, these two substitutions work synergistically.
Abstract: The well-known PB2 E627K substitution increased
New Threats from H7N9 Influenza Virus: Spread and Evolution of High- and Low-Pathogenicity Variants with High Genomic Diversity in Wave Five.
Abstract: Importantly, neuraminidase (NA) inhibitor (NAI) resistance (R292K in NA) and mammalian adaptation (e.g., E627K and A588V in PB2) mutations were found in a few non-human-derived HP-H7N9 strains.
Abstract: Notably, the NAI drug-resistant (R292K in NA) and mammalian-adapted (e.g., E627K in PB2) mutations were found in HP-H7N9 not only from human isolates but also from poultry and environmental isolates, indicating increased risks for human infections.
Challenge for One Health: Co-Circulation of Zoonotic H5N1 and H9N2 Avian Influenza Viruses in Egypt.
Abstract: The H5N1 viruses acquired enhanced bird-to-human transmissibility by (1) altering amino acids in hemagglutinin (HA) that enable binding affinity to human-type receptors, (2) loss of the glycosylation site and 130 loop in the HA protein and (3) mutation of E627K in the PB2 protein to enhance viral replication in mammalian hosts.
Introduction: Most Egyptian H5N1 viruses possess two other mutations that may facilitate their transmissibility and replication in mammals: (1) the deletion in the 130 loop (129Delta) with a concurrent loss of glycosylation mutation (T156A) in the HA and (2) E627K mutation in the PB2 protein.
Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets.
Abstract: This A/H5N6 virus possessed high polymerase activity, mediated by the E627K substitution in the PB2 protein, which corresponds to only one biological trait out of the three that were previously shown to confer airborne transmissibility to A/H5N1 viruses between ferrets.
Introduction: While our study suggests that the public health risk posed by this A/H5N6 virus is low, the A/H5N6 GZ/14 showed a high polymerase activity mediated by the E627K substitution in Result: A/H5N6 GZ/14 possesses a high polymerase activity, mediated by the E627K substitution in PB2.
Result: These observations demonstrated that the high polymerase activity of A/H5N6 GZ/14 was mediated by the E627K substitution in PB2.
PB2 and HA mutations increase the virulence of highly pathogenic H5N5 clade 2.3.4.4 avian influenza virus in mice.
Abstract: After two passages, we obtained a mouse-adapted H5N5 virus that contained single amino acid substitutions in the PB2 (E627K) and hemagglutinin (HA) (F430L) proteins.
Abstract: Furthermore, we found that PB2-E627K enhanced viral replication kinetics in vitro and in vivo.
Abstract: The 50% mouse lethal dose (MLD50) of the H5N5 virus containing the PB2-E627K substitution or the HA-F430L substitution was reduced 1000-fold or 3.16-fold, respectively.
Abstract: These results suggest that the PB2-E627K and
Potential Pandemic of H7N9 Avian Influenza A Virus in Human.
PMID: 30533399
2018
Frontiers in cellular and infection microbiology
Result: E/D627K/N and D701N in PB2 ha
Discussion: E627K in PB2, which is the best characterized mammalian adaptive mutation (de Wit et al.,), has very high proportions only in human-isolated H7N9 viruses.
Discussion: Amino acid changes E/D627K/N and D701N in PB2 were shown to be critical adaptations for infecting mammals (Subbarao et al.,; Hatta et al.,; Gabriel et al.,; Li et al.,).
Discussion: The D701N substitution in PB2 was found to increase virulence, and to expand the host range of avian H5N1 to mammals in the absence of E627K (Steel et al.,).
IV mutation literature information.
PMID: 
2019
Emerging microbes & infections
Browser Board
Co-occurred Entities
Filtrator
ViMRT