期刊
VIRUS RESEARCH
卷 189, 期 -, 页码 79-86出版社
ELSEVIER
DOI: 10.1016/j.virusres.2014.05.001
关键词
2009 A (H1N1); D222N; HA receptor binding site; Pathogenicity
类别
资金
- National Natural Science Foundation of China [31172323, 31172324]
- Chinese National High-tech R&D Program (863 Program) [2012AA101303]
- National Basic Research Program (973 Program) [2011CB504702]
- Graduate Innovation Foundation of China Agricultural University [2013YJ005]
The D222N hemagglutinin (HA) mutation within the receptor-binding site was detected with higher frequencies in severe cases of 2009 pandemic H1N1 (pdmH1N1) infections. The impact of this mutation was investigated in vitro and in vivo using recombinant viruses. The recombinant D222N virus grew to significantly lower viral titers than the WT in A549 but not in MOCK cells. A dose-dependent glycan array analysis with the D222N virus showed a modest increase in the binding avidity to human-like (alpha-2,6 sialylated glycan) receptors and avian-like (alpha-2,3 sialylated glycan) receptors than the WT virus. The D222N HA mutation resulted in slight weight loss, lower lung titers, inflammatory cytokines and alveolar inflammation in mice than the WT virus. This may or may not be associated with severe clinical outcomes reported in humans. (C) 2014 Elsevier B.V. All rights reserved.
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