Glycosylation of the hemagglutinin protein of H9N2 subtype avian influenza virus influences its replication and virulence in mice  

作　　者：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 

机构地区：[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

出　　处：《Journal of Integrative Agriculture》2019年第7期1443-1450,共8页农业科学学报（英文版）

基　　金：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);the High-Level Talents and Innovative Team Recruitment Program of the Shandong Academy of Agricultural Sciences,China

摘　　要：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 H9 N2 viruses for the potential N-linked glycosylation sites in HA proteins,and explored any important role of some glycosylation sites.HA genes of 19 H9 N2 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 N200 Q 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 H9 N2 viruses in mammals.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 H9 N2 viruses for the potential N-linked glycosylation sites in HA proteins, and explored any important role of some glycosylation sites. HA genes of 19 H9 N2 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 N200 Q 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 H9 N2 viruses in mammals.

关 键 词：H9N2 AIV HEMAGGLUTININ N-LINKED GLYCOSYLATION receptor affinity MICE 

分 类 号：S[农业科学]