Introduction: Our structure is the first deposited structure of a PB2 domain containing the pathogenicity determinant lysine 627 in the Protein Data Bank (2008 Apr 21) and we also revealed the RNA binding ability of this domain which is strengthened by the E627K mutation.
Introduction: The crystal structures of the large C-terminal domain of PB2, including this E627K mutation, which enables human infection, were reported by us and other.
Discussion: E627K mutation dramatically increased basic charge on the surface.
Discussion: It has been well known that the electrostatic surface change by the single E627K mutation enhanced the virulence, though it is still open question what is the role of K627 in the RNP complex.
Human H7N9 avian influenza virus infection: a review and pandemic risk assessment.
Abstract: Infection in Ratitae species may lead to the selection of PB2-E627K and PB2-D701N mutants and the conversion of nH7N9 to a highly pathogenic avian influenza virus.
Abstract: nH7N9 isolated from humans contains features related to adaptation to humans, including a Q226L mutation in the hemagglutinin cleavage site and E627K and D701N mutations in the PB2 protein.
Introduction: Influenza infection of ostrich and emu can lead to the selection of PB2-E627K and PB2-D701N m
H4N8 subtype avian influenza virus isolated from shorebirds contains a unique PB1 gene and causes severe respiratory disease in mice.
Introduction: However, point mutations of known molecular markers, such as PB2 E627K / D701N/ E677G, PB1-F2 N66S, and PA T97I, produced no significant change in pathogenicity when incorporated in pH1N1 individually.
Analysis by single-gene reassortment demonstrates that the 1918 influenza virus is functionally compatible with a low-pathogenicity avian influenza virus in mice.
Abstract: This attenuation could be corrected by the single E627K amino acid change, further confirming the importance of this change in mammalian adaptation and mouse pathogenicity.
V292I mutation in PB2 polymerase induces increased effects of E627K on influenza H7N9 virus replication in cells.
Abstract: Although the PB2 E627K amino acid substitution enhanced viral polymerase activity and replication, none of the single mutations of mouse adapted PB2 could confer increased virulence on the SD16 backbone.
Abstract: Five amino acid substitutions were found in the genome of SD16-MA compared with SD16 virus: PB2 (M147L, V250G and E627K), HA (L226Q) and M1 (R210K).
Abstract: The combination of M147L and E627K significantly enhanced viral replication ability and virulence in mice.
Discussion: After adaptati
PB2 residue 158 is a pathogenic determinant of pandemic H1N1 and H5 influenza a viruses in mice.
Abstract: Our data also show that PB2-E158G had a much stronger influence on the RNA replication and pathogenesis of H1N1pdm viruses than PB2-E627K, which is a known pathogenic determinant.
Influenza A virus NS1 gene mutations F103L and M106I increase replication and virulence.
Introduction: Key mutations in the PB2 gene increased pathogenicity and viral transmission such as E627K and D701N and mutation sites in H3 HA1 and HA2 subunits, G218W and T156N respectively, have been shown to affect both growth and virulence in the mouse.
V292I mutation in PB2 polymerase induces increased effects of E627K on influenza H7N9 virus replication in cells.
PMID: 21816827
2011
The Journal of biological chemistry
Abstract: 37 and 42C), whereas the human E627K mutant drastically lost activity at these high temperatures.
Abstract: Importantly, the E627K mutation elevates apparent K(cat) at low temperatures with little effect on K(m), suggesting that the E627K mutation alters the biochemical steps involved in enzyme catalysis rather than the interaction with the incoming NTP.
Abstract: Second, our steady-state kinetics data revealed that the human E627K mutant polymerase is catalytically more active than the avian Glu-627 polymerase at 34C.
Abstract: Third, this temperature-dependent kinetic impact of the human E627K mutation was also observed with different RNA templates, with different primers and also in the presence of nucleoprotein.
Molecular determinants of adaptation of highly pathogenic avian influenza H7N7 viruses to efficient replication in the human host.
Abstract: These in vitro studies confirmed the roles of the E627K substitution in basic polymerase 2 (PB2) and the A143T substitution in HA in pathogenicity observed in a mouse model previously.
Abstract: With the exception of PB2 E627K, all substitutions contributing to enhanced replication of the fatal case virus in vitro were present in poultry viruses prior to transmission to the human fatal case, indicating that viruses with enhanced replication efficiency in the mammalian host can be generated in poultry.
IV mutation literature information.
PMID: 
2013
PloS one
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