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-1beta, IL-6, IL-8, IL-10, MIP-1beta, and MIP-1alpha. 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.
Rabablert
Jundee
J
Center for Vaccine Development, Institute of Science and Technology, Mahidol University, Nakhon Pathom, and Department of Microbiology, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand.
Wasi
Chantapong
C
Kinney
Richard
R
Kasisith
Jitra
J
Pitidhammabhorn
Dhanesh
D
Ubol
Sukathida
S
D017209:Apoptosis; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003716:Dengue Virus / Q000472:pathogenicity* / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005416:Flavivirus / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D014765:Viral Vaccines; D014779:Virus Replication
D016207:Cytokines; D011506:Proteins; D014765:Viral Vaccines