The Relationship Between Nucleotide Mutations And Virulence Of Dengue Virus Under The Selection Pressure Of Host

Like other arboviruses, dengue virus (DENV) is maintained in nature by cyclingbetween vertebrate hosts and mosquito vectors. The number of dengue virus lineageshas been increasing over time. Recently, arboviruses outbreaks demonstrate thepotential of these pathogens for expansion and emergence, such as dengue virusremain persists and endemic in many areas, the need to better understand the selectivepressures that dengue virus population diversification maybe cause severity disease.Specifically, comprehensive understand of host-virus interactions and therelationships between variation and virulence.The main goal of this study was to identify the relationships between the geneticdiversity and virulence of dengue virus passaged between in vivo and vitro cells tosimulate natural alternation and contrasted the results with those for populationsfitness was measured with one-step growth curves, mouse neurovirulence and vectortransmissibility also were determined, and mutations were evaluated by nucleotidesequencing.The main results of this study are as follows: 1. The relationship between nucleotide mutations and virulence of dengue virusin vitro cells.The results demonstrated that fitness decreases occurred in alternating passage,but exclusive passage exhibited fitness gains to the host cell. Moreover, alternatelypassaged viruses led to a significant decreasing in other phenotype than continuouslypassaged strains. A comparison of the amino acid sequences of the parent andpassaged variants revealed that specialized viruses passaged in C6/36cellsaccumulated fewer mutations than those passaged in either Huh7cells or inalternation. Interesting, the substitution of Arg-E307for Lys and NS4B (Asn)acquired Asp, which could effect on virulence attenuating. In turn, the substitution ofIle for Thr-E155, Phe for Ser-E186, and Arg for Gln-E293could cause virulenceincreasing.2. The relationship between nucleotide mutations and virulence of dengue virusin vivo by host alternation.Increasing adaptation fitness and producing higher viremias happened on the4thalternating passage terminated in sucking mice variant(P4-Alt mice virus variant). At the sametime, P4-Alt mice virus variant led to a significant gains in other phenotype than parentstrains. A comparison of the amino acid sequences of the parent and passaged variantsrevealed that P4-Alt mice virus variant accumulated many mutations.Which thesubstitution of M、E71、E129、E390、E491、NS1-190and NS2A-34could causevirulence increasing. These results provide insights into the likelihood and extent ofshifts DENV virulence.These results provide insights into the likelihood and extent of shifts DENVvirulence. Therefore, understanding the genetic relationships and phenotypicdifferences in passaged variants may provide valuable insight into DENV emergenceand guide monitoring of future outbreaks.