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.,).
Unexpected infection outcomes of China-origin H7N9 low pathogenicity avian influenza virus in turkeys.
Introduction: The E627K (PB2 gene) polymorphism has been reported in in many human isolates with continuing evolution evident at the full-genome level in both human and poultry isolates.
Prerequisites for the acquisition of mammalian pathogenicity by influenza A virus with a prototypic avian PB2 gene.
Abstract: The MVV mutations caused no weight loss in mice, but they did allow replication in infected lungs, and the viruses acquired fatal mammalian pathogenic mutations such as Q591R/K, E627K, or D701N in the infected lungs.
Introduction: Amino acid position 627 on PB2 is located in the C-terminal RNA-binding domain, and the E627K mutation is known to increase both RNA binding and polymerase activity, increasing viral replication efficiency at 33 C, the approximate temperature of the human upper respiratory tract.
Introduction: Diverse mutations in the polymerase subunits that determine the mammalian pathogenicity of AIV have been reported, and E627K in PB2 is considered a key mutation.
Introduction: Furthermore, the
Co-expression of sialic acid receptors compatible with avian and human influenza virus binding in emus (Dromaius novaehollandiae).
Abstract: Since 2006, several reports of IAV isolations from emus have surfaced and avian influenza infection of emus can lead to the selection of mammalian like PB2-E627K and PB2-D701N mutants.
Genetic properties and pathogenicity of a novel reassortant H10N5 influenza virus from wild birds.
Abstract: After sequential passage in mice, mouse-adapted viruses bearing mutations PB2-E627K and HA-G218E were generated.
Identification of Rare PB2-D701N Mutation from a Patient with Severe Influenza: Contribution of the PB2-D701N Mutation to the Pathogenicity of Human Influenza.
Introduction: A(H1N1)pdm09 virus has an avian-lineage PB2 gene that lacks the E627K and D701N substitutions that permit transmission and cooperate in pathogenesis of avian-origin influenza viruses in humans or other mammals.
Introduction: Many of these are located in the polymerase PB2 subunit, with E627K and D701N as the most prevalent mutations, which are rarely present in human circulating viruses.
Introduction: The minimal set of mutations required for airborne transmission of a H5N1 virus among ferrets included, in addition of the PB2-E627K change, mutation PB1-H99Y, both mutations together had a synergistic effect, increasin
Enhanced pathogenicity and neurotropism of mouse-adapted H10N7 influenza virus are mediated by novel PB2 and NA mutations.
PMID: 28597818
2017
The Journal of general virology
Abstract: Sequencing showed the absence of the widely recognized mammalian adaptation markers of E627K and D701N in PB2 in the mouse-adapted strain; instead, five amino acid mutations were identified: E158G and M631L in PB2; G218E in haemagglutinin (H3 numbering); and K110E and S453I in neuraminidase (NA).
Virulence of an H5N8 highly pathogenic avian influenza is enhanced by the amino acid substitutions PB2 E627K and HA A149V.
PMID: 28750900
2017
Infection, genetics and evolution
Abstract: Substitutions in the HA (A149V) and PB2 (E627K) proteins led to enhanced viral virulence in mice, the viruses displayed expanded tissue tropism, and increased replication kinetics in mammalian cells.
Abstract: The virulence of mouse-adapted virus was increased and adaptive mutations, HA (A149V) and PB2 (E627K), were detected after the ninth passage in each series of mice.
Rapid virulence shift of an H5N2 avian influenza virus during a single passage in mice.
Abstract: Our molecular analysis revealed that two amino acid changes in the polymerase complex (a glutamate-to-lysine substitution at position 627 of PB2 and a threonine-to-isoleucine substitution at position 97 of PA) were associated with the increased pathogenicity; the PB2 E627K mutation was responsible for the initial virulence conversion (0 to 100% lethality), while the PA T97I mutation acted as an accessory for the increased virulence.
Amino Acid Substitutions Associated with Avian H5N6 Influenza A Virus Adaptation to Mice.
Result: Additionally, the PB2 E627K mutation could increase the strength of polymerase nucleocapsid binding and modulate nucleocapsid inhibition via the pathogen sensor RIG-I.
Result: Alone or in combination with PB2 E627K, PA T97I was shown to enhance the polymerase activity, replication efficiency, and pathogenicity of influenza A virus to aid the adaptation of virus to mice, and this was also true for H5N2 and H7N9.
Result: Eight amino acid substitutions were identified, two in the HA subunit (I67V, R239H), two in the polymerase basic protein 2 (PB2) subunit (T23I,
ViMRT
IV mutation literature information.
PMID: 
2018
Frontiers in cellular and infection microbiology
