Neighboring mutation-mediated enhancement of dengue virus infectivity and spread.
EMBO Rep
; 23(11): e55671, 2022 11 07.
Article
em En
| MEDLINE
| ID: mdl-36197120
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Dengue
/
Vírus da Dengue
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article