Glycosylation on envelope glycoprotein of duck Tembusu virus affects virus replication in vitro and contributes to the neurovirulence and pathogenicity in vivo

Virulence

Hui Jin¹  Rui Luo¹  Peng Zhou¹  Dejian Liu¹  Xuyao Xiao¹  Yaqian Li¹  Huijun Zheng¹  Anan Jongkaewwattana² 

[1] State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, Chin;Key Laboratory of Preventive Veterinary Medicine in Hubei Province, the Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, Chin;Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (Biotec), National Science and Technology Development Agency (Nstda), Klong Nueng, Pathum Thani Thailan;

关键词: Duck Tembusu virus;    envelope protein;    glycosylation;    replication;    pathogenicity;   

DOI  :  10.1080/21505594.2021.1974329

来源: Taylor & Francis

【 摘 要 】

Duck Tembusu virus (DTMUV), an emergent flavivirus, causes domestic waterfowls to suffer from severe egg-drop syndrome and fatal encephalitis, greatly threatens duck production globally. Like other mosquito-borne flaviviruses, the envelope (E) protein of all DTMUV strains was N-glycosylated at the amino acid position 154. Thus far, the biological roles of DTMUV E glycosylation have remained largely unexplored. Herein, we demonstrated the key roles of E glycosylation in the replication and pathogenicity of DTMUV in ducks by characterizing the reverse-genetics-derived DTMUV wild-type MC strain and MC bearing mutations (N154Q and N154I) that abolish the E glycosylation. Our data showed that the disruption of E glycosylation could substantially impair virus attachment, entry, and infectivity in DEFs and C6/36 cells. Notably, ducks inoculated intracerebrally with the wild-type virus exhibited severe disease onset. In contrast, those inoculated with mutant viruses were mildly affected as manifested by minimal weight loss, no mortality, lower viral loads in the various tissues, and reduced brain lesions. Attenuated phenotypes of the mutant viruses might be partly associated with lower inflammatory cytokines expression in the brains of infected ducks. Our study offers the first evidence that E glycosylation is vital for DTMUV replication, pathogenicity, and neurovirulence in vivo.

【 授权许可】

CC BY