title: Naturally mutated envelope protein domain I of Chinese B dengue virus attenuated human dendritic cell maturation.
abstract: Dengue virus (DENV) can infect human dendritic cells (DCs), and cause a spectrum of clinical symptoms. Envelope protein of DENV contains three distinct domains, including domain I (DI), domain II (DII) and domain III (DIII), and plays important roles in receptor binding and induction of protective antibodies. Previously, a new DENV-2 type virus (named B strain) with eight gene mutations in DI of the envelope protein was isolated from a dengue hemorrhagic fever patient. BALB/c mice infected with DENV B strain showed more prolonged viremia than mice infected with the New Guinea C (NGC) strain. However, the mechanism of prolonged viremia was not determined. In this study, DI proteins derived from B and NGC strains of DENV were expressed in Rosetta (DE3) host bacteria and purified by affinity chromatography after refolding. A flow cytometry-based binding assay and confocal microscopy indicated that both proteins could bind to human DCs induced from peripheral blood mononuclear cells (PBMCs), but DI of the B strain had a lower affinity than DI of the NGC strain, and viable B virus also show less binding efficiency with DCs. In addition, DI of the NGC strain, but not the B strain, induced IL-12 secretion and phenotypic maturation of DCs, such as up-regulated expression of CD80, CD83, CD86 and HLA-DR. NGC strain could induce more virus specific IgM/IgG. These results suggest that the naturally mutated envelope protein DI of the Chinese B strain of DENV cannot induce DC maturation as high efficiency as that of NGC strain, which may be the partial reason that DENV B strain escapes immune recognition and induce prolonged viremia. The mutated B strain envelope protein is not a good candidate for subunit vaccine target.
authors.affiliation: Department of Immunology, Guiyang Medical College, Guiyang 550004, China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Li
authors.forename: Xulong
authors.initials: X
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zuo
authors.forename: Zhengling
authors.initials: Z
authors.lastname: Shang
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects*; D003716:Dengue Virus / Q000145:classification* / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D017434:Protein Structure, Tertiary; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D014764:Viral Proteins