Introduction: Independent examples of selection of the PB2-D701N mutation have also been observed, for example, in the nonpandemic avian origin European swine H1N1 viruses as well as in some HPAI H5N1 viruses.
Introduction: Residue 701, residing in a region of PB2 implicated in nuclear localization, has similarly been identified as a host-adaptive locus, with the D701N mutation increasing both replication in mice and transmission in guinea pigs.
Result: Again, to our surprise, introduction of the mammalian-adaptive PB2-E627K or -D701N mutation into the pandemic RNP significantly attenuated viral replication in mouse lung.
Result: CA09RNP-E627K and CA09RNP-
Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission.
Abstract: Here, using reverse genetics, mutations E627K, D701N, and E677G were introduced into the prototype S-OIV A/Netherlands/602/2009, and their effects on virus replication, virulence, and transmission were investigated.
Abstract: Mutations E627K and D701N caused increased reporter gene expression driven by the S-OIV polymerase complex.
Abstract: Mutations E627K and D701N in the PB2 protein have previously been identified as determinants of avian and pandemic influenza virus virulence in mammals.
Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E/701N.
Introduction: A mechanism has recently been proposed to explain the contribution of D701N to improved growth of a mouse adapted avian-like H7N7 virus, SC35M, in mammalian cell culture: D701N appears to enhance the binding of PB2 to importin alpha1 and correspondingly increase PB2 levels in the nucleus in mammalian, but not avian, cells.
Introduction: Our second hypothesis did prove correct in that combination of glutamic acid at 627 with an aspartic acid to asparagine change at position 701 rescues the phenotype of the 627E viruses: rPan99 virus with 627E+701N transmits with similar efficiency to the parental rPan99 virus, while the rVN1203 627E 701N virus transmits with higher efficiency than the wild-type strain.
Introduction: Similarly to E627K, a change of PMID: 18248089
2008
PLoS pathogens
Abstract: We show now that adaptive mutations D701N in PB2 and N319K in NP enhance binding of these proteins to importin alpha1 in mammalian cells.
Introduction: PB2 mutation D701N has also been implicated in the adaptation of H5N1 viruses to mammalian hosts but other mutations may be involved, too, notably PB2 mutation E627K.
Introduction: Interestingly, the authors of this study hypothesized that PB2 mutation D701N which is also a host range determinant as pointed out above, may affect the binding of importin alpha5 to PB2.
Introduction: Thus, in a comparative study of the avian str
Host determinant residue lysine 627 lies on the surface of a discrete, folded domain of influenza virus polymerase PB2 subunit.
Introduction: Subsequently it was shown that the substitution D701N significantly affects the interaction of PB2 with importin alpha1 in mammalian but not avian cells.
Discussion: In addition, the residues 701 and 714, whose mutation (respectively D701N and S714R) have been shown to affect polymerase activity in a laboratory model of adaptation of virulent strains from birds to mice, are located on the surface of the NLS-domain.
Discussion: Interestingly, in 3/4 cases retaining Glu627, but none of those with E627K, the D701N mutation was also found, leading to the suggestion that the latter mutation may compensate for the lack of change at position 627.
Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model.
IV mutation literature information.
PMID: 
2010
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