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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Virol
2011 ; 85
(4
): 1834-46
Nephropedia Template TP
gab.com Text
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NP body domain and PB2 contribute to increased virulence of H5N1 highly
pathogenic avian influenza viruses in chickens
#MMPMID21123376
Tada T
; Suzuki K
; Sakurai Y
; Kubo M
; Okada H
; Itoh T
; Tsukamoto K
J Virol
2011[Feb]; 85
(4
): 1834-46
PMID21123376
show ga
The molecular basis of pathogenicity of H5N1 highly pathogenic avian influenza
(HPAI) viruses in chickens remains largely unknown. H5N1
A/chicken/Yamaguchi/7/2004 virus (CkYM7) replicates rapidly in macrophages and
vascular endothelial cells in chickens, causing sudden death without fever or
gross lesions, while H5N1 A/duck/Yokohama/aq10/2003 virus (DkYK10) induces high
fever, severe gross lesions, and a prolonged time to death, despite the 98% amino
acid identity between the two viruses. To explore the molecular basis of this
difference in pathogenicity, a series of eight single-gene reassortant viruses
from these HPAI viruses were compared for pathogenicity in chickens. Two
reassortants possessing the NP or PB2 gene from DkYK10 in the CkYM7 background
reduced pathogenicity compared to other reassortants or CkYM7. Inversely,
reassortants possessing the NP or PB2 gene of CkYM7 in the DkYK10 background
(rgDkYK-PB2(Ck), rgDkYK-NP(Ck)) replicated quickly and reached higher titers than
DkYK10, accompanied by more rapid and frequent apoptosis of macrophages. The
rgDkYK-NP(Ck) and rgDkYK-PB2(Ck) reassortants also replicated more rapidly in
chicken embryo fibroblasts (CEFs) than did rgDkYK10, but replication of these
viruses was similar to that of CkYM7 and DkYK10 in duck embryo fibroblasts. A
comparison of pathogenicities of seven rgDkYK10 mutants with a single amino acid
substitution in NP(Dk) demonstrated that valine at position 105 in the NP(Ck) was
responsible for the increased pathogenicity in chickens. NP(Ck), NP(105V), and
PB2(Ck) enhanced the polymerase activity of DkYK10 in CEFs. These results
indicate that both NP and PB2 contribute to the high pathogenicity of the H5N1
HPAI viruses in chickens, and valine at position 105 of NP may be one of the
determinants for adaptation of avian influenza viruses from ducks to chickens.
|Amino Acid Sequence
[MESH]
|Animals
[MESH]
|Cell Line
[MESH]
|Chick Embryo
[MESH]
|Chickens/*virology
[MESH]
|Ducks/virology
[MESH]
|Fibroblasts/virology
[MESH]
|Humans
[MESH]
|Influenza A Virus, H5N1 Subtype/classification/genetics/metabolism/*pathogenicity
[MESH]