登革热病毒
传染性
生物
登革热
病毒学
克莱德
病毒
登革热疫苗
突变
抗体依赖性增强
基因型
寄主(生物学)
遗传学
基因
系统发育学
作者
Lu Chen,Xianwen Zhang,Xuan Guo,Wenyu Peng,Yibin Zhu,Zhaoyang Wang,Xi Yu,Huicheng Shi,Yuhan Li,Liming Zhang,Lei Wang,Penghua Wang,Gong Cheng
标识
DOI:10.15252/embr.202255671
摘要
Frequent turnover of dengue virus (DENV) clades is one of the major forces driving DENV persistence and prevalence. In this study, we assess the fitness advantage of nine stable substitutions within the envelope (E) protein of DENV serotypes. Two tandem neighboring substitutions, threonine to lysine at the 226th (T226K) and glycine to glutamic acid at the 228th (G228E) residues in the DENV2 Asian I genotype, enhance virus infectivity in either mosquitoes or mammalian hosts, thereby promoting clades turnover and dengue epidemics. Mechanistic studies indicate that the substitution-mediated polarity changes in these two residues increase the binding affinity of E for host C-type lectins. Accordingly, we predict that a G228E substitution could potentially result in a forthcoming epidemic of the DENV2 Cosmopolitan genotype. Investigations into the substitutions associated with DENV fitness in hosts may offer mechanistic insights into dengue prevalence, thus providing a warning of potential epidemics in the future.
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