Biological and structural characterization of a host-adapting amino acid in influenza virus.
Two amino acids (lysine at position 627 or asparagine at position 701) in the polymerase subunit PB2 protein are considered critical for the adaptation of avian influenza A viruses to mammals. However, the recently emerged pandemic H1N1 viruses lack these amino acids. Here, we report that a basic amino acid at position 591 of PB2 can compensate for the lack of lysine at position 627 and confers efficient viral replication to pandemic H1N1 viruses in mammals. Moreover, a basic amino acid at position 591 of PB2 substantially increased the lethality of an avian H5N1 virus in mice. We also present the X-ray crystallographic structure of the C-terminus of a pandemic H1N1 virus PB2 protein. Arginine at position 591 fills the cleft found in H5N1 PB2 proteins in this area, resulting in differences in surface shape and charge for H1N1 PB2 proteins. These differences may affect the protein's interaction with viral and/or cellular factors, and hence its ability to support virus replication in mammals.
Yamada
Shinya
S
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Hatta
Masato
M
Staker
Bart L
BL
Watanabe
Shinji
S
Imai
Masaki
M
Shinya
Kyoko
K
Sakai-Tagawa
Yuko
Y
Ito
Mutsumi
M
Ozawa
Makoto
M
Watanabe
Tokiko
T
Sakabe
Saori
S
Li
Chengjun
C
Kim
Jin Hyun
JH
Myler
Peter J
PJ
Phan
Isabelle
I
Raymond
Amy
A
Smith
Eric
E
Stacy
Robin
R
Nidom
Chairul A
CA
Lank
Simon M
SM
Wiseman
Roger W
RW
Bimber
Benjamin N
BN
O'Connor
David H
DH
Neumann
Gabriele
G
Stewart
Lance J
LJ
Kawaoka
Yoshihiro
Y
D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D020836:Protein Structure, Quaternary; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics; D014774:Virulence / Q000235:genetics; D014779:Virus Replication
D000596:Amino Acids; C502893:PB2 protein, influenza virus; D014764:Viral Proteins