Introduction: In addition to human receptor binding characteristics, human H7N9 isolates often possess several other markers of mammalian adaptation, such as E627K and D701N in the PB2 protein.
Evolved avian influenza virus (H7N9) isolated from human cases in a middle Yangtze River city in China, from February to April 2017.
Result: Importantly, the PB2 gene Ala588Val and both Ala588Val/Glu627Lys mutations in the H7N9 virus have been demonstrated to enhance virulence in mice and the transmission of influenza viruses in mammals.
Result: In addition, two of the strains, A/changsha/34/2017 and A/changsha/72/2017, acquired both Ala588Val/Glu627Lys mutations.
Table: Glu627Lys
Discussion: However, a minority of successfully infections are presented with deficiency of PB2 E627K mutant.
Discussion: Moreover, PB2 Ala588Val showed more efficiently enhanced virulence than the
The PB2 Polymerase Host Adaptation Substitutions Prime Avian Indonesia Sub Clade 2.1 H5N1 Viruses for Infecting Humans.
Discussion: E627K is the most well recognized adaptation marker for human infections caused by avian H5N1, H7N7 and H7N9 viruses.
Discussion: Here, we propose that K526R is a pre-existing mammalian adaptive marker of avian H5N1 viruses in the Indonesia lineage and provide the following supporting evidence: (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-
Adaptive amino acid substitutions enhance the virulence of an avian-origin H6N1 influenza virus in mice.
PMID: 31200112
2019
Infection, genetics and evolution
Abstract: The results showed that PB2 (L193H and E627K), PA (S709F) and HA (V127I) proteins had multiple amino acid substitutions.
V292I mutation in PB2 polymerase induces increased effects of E627K on influenza H7N9 virus replication in cells.
Result: As shown in Table 1, two H9N2 viruses, A/chicken/Henan/5/1998 [CK/5(H9N2)] and A/chicken/Guangxi/9/1999 [CK/9(H9N2)], isolated in the 1990s did not acquire the PB2 E627K mutation even after being passaged six times in MDCK cells.
Result: Because our study in mice showed that PA is important for PB2 E627K acquisition during mammalian adaptation of PG/S1421(H7N9), we next investigated whether PG/S1421(H7N9), CK/5(H9N2), and their reassortants had different RNP activities in HEK293T cells.
Result: CK/5(H9N2), a representative of viruses that maintain a stable PB2 627E during replication in mammals, was selected with PG/S1421(H7N9) to form a model virus pair to investigate the viral factors that drive the emergence of the
Mammalian-adaptive mutation NP-Q357K in Eurasian H1N1 Swine Influenza viruses determines the virulence phenotype in mice.
Introduction: Of these, the E627K and/or D701N mutations in the PB2 protein are critical in the mammalian adaptation of avian influenza viruses.
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.
Discussion: PB2-E627K mutation alters polymerase activity by affecting the interaction of PB2 with NP and exhib
Discussion: Increased polymerase activity conferred by other mutations on PB2, such as PB2-E627K, has been shown to be crucial for AIVs to adapt to mammalian hosts.
Synergistic PA and HA mutations confer mouse adaptation of a contemporary A/H3N2 influenza virus.
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.
A study of the relationship between human infection with avian influenza a (H5N6) and environmental avian influenza viruses in Fujian, China.