title: Infection of hepatocytes with 17-D vaccine-strain yellow fever virus induces a strong pro-inflammatory host response.
abstract: Yellow fever virus (YFV) causes serious disease in endemic areas of South America and Africa, even though a very well tolerated vaccine is available. YFV primarily targets the liver where as many as 80 % of hepatocytes may be involved during infection. The objective of this project was to compare and contrast the cytokine response from hepatocytes infected with either wild-type (Asibi) or vaccine (17-D-204) strains of YFV, with the goal of identifying responses that might be correlated with disease severity or vaccine efficacy. We report here that PH5CH8 hepatocytes support a productive infection with both wild-type and vaccine-strain YFV. Infection with either virus resulted in elevated expression of several pro- and anti-inflammatory cytokines [interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10 and tumour necrosis factor-α) with a corresponding increase in transcription. Hepatocytes infected with vaccine virus had a more profound response than did cells infected with wild-type virus. Pre-stimulation of hepatocytes with IL-6 resulted in reduced viral titres, elevated concentrations of cytokines released from Asibi virus-infected cells and improved cell viability in cells infected with 17-D virus. Data reported here suggest that 17-D virus stimulates an appropriate antiviral inflammatory response in hepatocytes, while Asibi virus can attenuate the host response. These data identify potential mechanisms that are associated with increased virulence in wild-type virus infections and also provide clues towards potential immune-response limitations that may be associated with vaccine-related adverse events.
authors.affiliation: Department of Pathology and Institute for Human Infection and Immunity, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77550, USA.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Woodson
authors.affiliation: Department of Pathology and Institute for Human Infection and Immunity, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77550, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Holbrook
mesh_terms: D002460:Cell Line; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism*; D022781:Hepatocytes / Q000276:immunology* / Q000821:virology*; D006801:Humans; D022341:Yellow Fever Vaccine / Q000276:immunology; D015005:Yellow fever virus / Q000276:immunology*
chemical_list: D016207:Cytokines; D022341:Yellow Fever Vaccine