title: Hemagglutinin mutation D222N of the 2009 pandemic H1N1 influenza virus alters receptor specificity without affecting virulence in mice.
abstract: 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 MDCK cells. A dose-dependent glycan array analysis with the D222N virus showed a modest increase in the binding avidity to human-like (α-2,6 sialylated glycan) receptors and avian-like (α-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.
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, 17 Qinghua Donglu, Beijing 100193, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Kong
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, 17 Qinghua Donglu, Beijing 100193, China.
authors.forename: Linqing
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, 17 Qinghua Donglu, Beijing 100193, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, 17 Qinghua Donglu, Beijing 100193, China.
authors.forename: Huijie
authors.initials: H
authors.lastname: Gao
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, 17 Qinghua Donglu, Beijing 100193, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wei
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, 17 Qinghua Donglu, Beijing 100193, China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Sun
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, 17 Qinghua Donglu, Beijing 100193, China.
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, 17 Qinghua Donglu, Beijing 100193, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Liu
authors.affiliation: China Rural Technology Development Center, Beijing, 100045, China.
authors.forename: Guangpeng
authors.initials: G
authors.lastname: Ma
authors.affiliation: Key Laboratory of Animal Epidemiology and Zoonosis, Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, 17 Qinghua Donglu, Beijing 100193, China. Electronic address: pujuan@cau.edu.cn.
authors.forename: Juan
authors.initials: J
authors.lastname: Pu
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001835:Body Weight; D002460:Cell Line; D016207:Cytokines / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D008168:Lung / Q000473:pathology / Q000821:virology; D008807:Mice, Inbred BALB C; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000821:virology; D019562:Viral Load; D014774:Virulence; D053585:Virus Attachment
chemical_list: D016207:Cytokines; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D050505:Mutant Proteins
keywords: 2009 A (H1N1); D222N; HA receptor binding site; Pathogenicity