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Volume 92, Issue 10

Infection of hepatocytes with 17-D vaccine-strain yellow fever virus induces a strong pro-inflammatory host response Free

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.

  • Received:
  • Accepted:
  • Published Online:
© 2011 SGM
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2011-10-01
2024-04-19
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Infection of hepatocytes with 17-D vaccine-strain yellow fever virus induces a strong pro-inflammatory host response
J. Gen. Virol. 92, 2262 (2011); https://doi.org/10.1099/vir.0.031617-0
/content/journal/jgv/10.1099/vir.0.031617-0
/content/journal/jgv/10.1099/vir.0.031617-0
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