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Journal of Integrative Agriculture  2019, Vol. 18 Issue (7): 1443-1450    DOI: 10.1016/S2095-3119(19)62669-9
Special Focus: Animal influenza virus Advanced Online Publication | Current Issue | Archive | Adv Search |
Glycosylation of the hemagglutinin protein of H9N2 subtype avian influenza virus influences its replication and virulence in mice
TAN Liu-gang1*, CHEN Zhao-kun2*, MA Xin-xin3, HUANG Qing-hua1, SUN Hai-ji2, ZHANG Fan2, YANG Shao-hua1, XU Chuan-tian1, CUI Ning        
1 Shandong Key Laboratory of Animal Disease Control & Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan 250100, P.R.China
2 College of Life Sciences, Shandong Normal University, Jinan 250014, P.R.China
3 Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Shandong Agricultural University, Tai’an 271018, P.R.China
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N-Linked glycosylation of hemagglutinin (HA) has been demonstrated to regulate the virulence and receptor-binding specificity of avian influenza virus (AIV).  In this study, we characterized the variation trend of naturally isolated H9N2 viruses for the potential N-linked glycosylation sites in HA proteins, and explored any important role of some glycosylation sites.  HA genes of 19 H9N2 subtype AIV strains since 2001 were sequenced and analyzed for the potential glycosylation sites.  The results showed that the viruses varied by losing one potential glycosylation site at residues 200 to 202, and having an additional one at residues 295 to 297 over the past few years.  Further molecular and single mutation analysis revealed that the N200Q mutation lost an N-linked glycosylation at positions 200 to 202 of the HA protein and affected the human-derived receptor affinity.  We further found that this N-linked glycosylation increased viral productivity in the lung of the infected mice.  These findings provide a novel insight on understanding the determinants of host adaption and virulence of H9N2 viruses in mammals.
Keywords:  H9N2 AIV        hemagglutinin        N-linked glycosylation              receptor affinity        mice  
Received: 28 November 2018   Online: 24 January 2019   Accepted:
Fund: The study was supported by the National Key R&D Program of China (2016YFD0500201), the Natural Science Foundation of Shandong Province, China (ZR2017BC094), the earmarked fund for China Agriculture Research System (CARS-41-Z10), and the High-Level Talents and Innovative Team Recruitment Program of the Shandong Academy of Agricultural Sciences, China.
Corresponding Authors:  Correspondence XU Chuan-tian, E-mail:; CUI Ning, E-mail:   
About author:  * These authors contributed equally to this study.

Cite this article: 

TAN Liu-gang, CHEN Zhao-kun, MA Xin-xin, HUANG Qing-hua, SUN Hai-ji, ZHANG Fan, YANG Shao-hua, XU Chuan-tian, CUI Ning. 2019. Glycosylation of the hemagglutinin protein of H9N2 subtype avian influenza virus influences its replication and virulence in mice. Journal of Integrative Agriculture, 18(7): 1443-1450.

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