Attenuating characteristics of DEN-2 PDK53 in flavivirus-naïve peripheral blood mononuclear cells

A live-attenuated DEN-2 virus, DEN-2 strain 16681-PDK53, has been found to be attenuated for both humans and mice with an unknown mechanism. To partially answer this question, responses of flavivirus-naïve primary human PBMC to infection with attenuated DEN-2 PDK53 (D2/IC-VV45R) virus and its parental, virulent DEN-2 16681 virus (D2/IC-30P-A) were investigated at the cellular and genetic levels using cDNA array analysis. Both DEN-2 viruses produced similar replication kinetics in flavivirus-naïve PBMC. In contrast, virulent DEN-2 virus caused a higher percentage of apoptotic death. A macro-array analysis showed that the virulent D2/IC-30P-A virus induced changes in the expression of a greater number of genes than did the attenuated D2/IC-VV45R virus, 31 genes versus 19 genes, respectively, by 24 h post-infection. Interestingly, both viruses stimulated cytokines known to be virulence factors for DEN virus infection, such as IL-1β, IL-6, IL-8, IL-10, MIP-1β, and MIP-1α. The virulent virus additionally up-regulates immune suppression factors and down-regulates immune activator and growth factors. In conclusion, our data demonstrated that D2-PDK53 effected less change in PBMC than D2-16681 in terms of observable cellular effect and expression of cytokine and chemokine related genes.