Neighboring mutation‐mediated enhancement of dengue virus infectivity and spread

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.

The Role of Noncoding RNA in the Transmission and Pathogenicity of Flaviviruses

“…Arthropod-borne flaviviruses were initially discovered within arthropods and are naturally transmitted through the bites of hematophagous insects such as mosquitoes, ticks, and sandflies [ 9 , 10 ]. Over the past few decades, factors such as global warming, increased human mobility, and viral evolution have led to the expanding reach of flavivirus infections [ 11 , 12 , 13 ]. Several significant pathogens, including dengue virus (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), yellow fever virus (YFV), and tick-borne encephalitis virus (TBEV), have consecutively emerged and caused outbreaks of both emerging and re-emerging infectious diseases in various regions, posing a substantial threat to global public health.…”