title: Replication of chimeric yellow fever virus-dengue serotype 1-4 virus vaccine strains in dendritic and hepatic cells.
abstract: ChimeriVax-dengue (DEN) viruses are live attenuated vaccine candidates. They are constructed by replacing the premembrane (prM) and envelope (E) genes of the yellow fever (YF) 17D virus vaccine with the corresponding genes from wild-type DEN viruses (serotypes 1-4) isolated from humans. In this study, the growth kinetics of ChimeriVax-DEN1-4 and parent viruses (wild-type DEN-1-4 and YF 17D) were assessed in human myeloid dendritic cells (DCs) and in three hepatic cell lines (HepG2, Huh7, and THLE-3). In DC, ChimeriVax-DEN-1-4 showed similar growth kinetics to their parent viruses, wild-type DEN virus (propagated in Vero cells), or YF 17D virus (peak titers ~3-4.5 log(10) plaque-forming units (PFU)/mL at 48-72 hours post-infection). Parent wild-type DEN-1-4 viruses derived from C6/36 mosquito cells did not show any growth at a multiplicity of infection of 0.1 in DCs, except for DEN-2 virus, which grew to a modest titer of 2.5 log(10) PFU/mL at 48 hours post-infection. ChimeriVax-DEN1-4 grew to significantly lower titers (2-5 log(10) PFU/mL) than YF 17D virus in hepatic cell lines THLE-3 and HepG2, but not in Huh7 cells. These experiments suggest that ChimeriVax-DEN1-4 viruses replicate similarly to YF-VAX in DCs, but at a lower level than YF 17D virus in hepatic cell lines. The lack of growth of chimeric viruses in human hepatic cells suggests that these viruses may be less hepatotropic than YF 17D virus vaccine in humans.
authors.affiliation: Institute of Virology, Medical University of Vienna, Vienna, Austria.
authors.forename: Samantha
authors.initials: S
authors.lastname: Brandler
authors.forename: Nathan
authors.initials: N
authors.lastname: Brown
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Ermak
authors.forename: Fred
authors.initials: F
authors.lastname: Mitchell
authors.forename: Megan
authors.initials: M
authors.lastname: Parsons
authors.forename: Zhenxi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jean
authors.initials: J
authors.lastname: Lang
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Monath
authors.forename: Farshad
authors.initials: F
authors.lastname: Guirakhoo
mesh_terms: D000330:Aedes / Q000821:virology*; D000818:Animals; D002460:Cell Line; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D003713:Dendritic Cells / Q000821:virology*; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology*; D007303:Insect Vectors / Q000821:virology; D014613:Vaccines, Attenuated / Q000235:genetics; D014765:Viral Vaccines / Q000276:immunology; D014779:Virus Replication; D053060:West Nile Virus Vaccines
chemical_list: C445780:ChimeriVax; D004279:DNA, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines; D053060:West Nile Virus Vaccines