Amino acid sequence analysis and identification of mutations under positive selection in hemagglutinin of 2009 influenza A (H1N1) isolates.
The 2009 flu pandemic is caused by a new strain of influenza A (H1N1) virus, A/H1N1/09. With its high transmissibility, this novel virus has caused a pandemic and infected over 600,000 people globally. By comparing the hemagglutinin (HA) gene and protein sequences among over 700 A/H1N1/09 isolates, mutations in the receptor-binding sites and antigenic epitope regions were identified. Among these mutations, T220 and E/G239 were found to be strongly positively selected over the course of spreading of the A/H1N1/09 virus worldwide. Interestingly, both sites are located in the highly variable epitope regions of HA1, and residue 239 also plays an important role in the receptor-binding process. Further analyses demonstrated that the percentage of T220 mutants among all isolates increased rapidly during the evolution, and that an E/G239 mutation could decrease the binding affinity of the virus with its cellular receptor. Thus, due to a potential functional importance of residues 220 and 239, mutations at these sites, as well as the significant of positive selection on these sites deserves more attention, while new vaccines and therapeutic drugs are developed against this novel virus.
Ding
Xiaofan
X
Key Laboratory of Tropical Disease Control, Ministry of Education, Sun Yat-Sen University, 74 Zhongshan Road II, Guangzhou, Guangdong, China.
Jiang
Lifang
L
Ke
Changwen
C
Yang
Zhan
Z
Lei
Chunliang
C
Cao
Kaiyuan
K
Xu
Jun
J
Xu
Lin
L
Yang
Xingfen
X
Zhang
Yonghui
Y
Huang
Ping
P
Huang
Weijun
W
Zhu
Xun
X
He
Zhenjian
Z
Liu
Liping
L
Li
Jun
J
Yuan
Jie
J
Wu
Jueheng
J
Tang
Xiaoping
X
Li
Mengfeng
M
D000595:Amino Acid Sequence; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D007251:Influenza, Human / Q000821:virology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D012641:Selection, Genetic; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein
D019267:Hemagglutinin Glycoproteins, Influenza Virus
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