Basic Amino Acid Substitution at Residue 367 of the Envelope Protein of Tembusu Virus Plays a Critical Role in Pathogenesis
| العنوان: | Basic Amino Acid Substitution at Residue 367 of the Envelope Protein of Tembusu Virus Plays a Critical Role in Pathogenesis |
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| المؤلفون: | Zhuolin Li, Pinghuang Liu, Xue Sun, Lijiao Zhang, Jun Wang, Yanxin Cao, Mengxu Sun, Jingliang Su, Fengli Liu, Ziding Yu |
| المصدر: | Journal of Virology. 94 |
| بيانات النشر: | American Society for Microbiology, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0303 health sciences, Mutation, biology, 030306 microbiology, Immunology, Virulence, Mutagenesis (molecular biology technique), Viremia, medicine.disease_cause, biology.organism_classification, medicine.disease, Microbiology, Virology, Virus, Neutralization, 03 medical and health sciences, Flavivirus, Viral replication, Insect Science, medicine, 030304 developmental biology |
| الوصف: | Tembusu virus (TMUV) is a flavivirus responsible for panzootic outbreaks of severe egg-drop and fatal encephalitis of domestic waterfowl in China. Although TMUV can be attenuated by in vitro passaging, experimental evidence supporting the role of specific genetic changes in virulence attenuation is currently lacking. Here, we performed site-directed mutagenesis on five envelope (E) protein amino acid residues in accordance with the attenuated TMUV generated in our recent study. Our results showed that the Thr-to-Lys mutation of residue 367 in E protein (E367) plays a predominant role in viral cell adaptation and virulence attenuation in ducks compared with mutations in other residues. We further demonstrated that the positively charged basic amino acid substitution at E367 enhanced the viral binding affinity for glycosaminoglycans (GAGs) and reduced viremia levels and the efficiency of replication in major target organs in subcutaneously inoculated ducks. Interestingly, the T367K mutation increased viral neutralization sensitivity to the early immune sera. Together, our findings provide the first evidence that a basic amino acid substitution at E367 strongly impacts the in vitro and in vivo infection of TMUV.IMPORTANCE Outbreaks of Tembusu virus (TMUV) infection have caused huge economic losses in the production of domestic waterfowl since the virus was first recognized in China in 2010. To control TMUV infection, a live-attenuated vaccine candidate of TMUV was developed in our previous study, but the mechanisms of virulence attenuation are not fully understood. Here, we found that the Thr-to-Lys substitution at E367 is a crucial determinant of TMUV virulence attenuation in ducks. We demonstrated that the T367K mutation attenuates TMUV through reducing viral replication in the blood, brain, heart (ducklings), and ovaries. These data provide new insights into understanding the pathogenesis of TMUV and the rational development of novel TMUV vaccines. |
| تدمد: | 1098-5514 0022-538X |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::d84c98c3e305bbf9d2f3c5872ab3dc72 https://doi.org/10.1128/jvi.02011-19 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........d84c98c3e305bbf9d2f3c5872ab3dc72 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10985514 0022538X |
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