No evidence of the unfolded protein response in patients with chronic hepatitis C virus infection

Stuart McPherson1, Elizabeth E Powell, Helen D Barrie

  • 1Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.

Insights

The unfolded protein response (UPR) is not activated in patients with chronic Hepatitis C virus (HCV) infection. This suggests the UPR may not significantly contribute to liver injury in chronic HCV.

Area of Science:

  • Hepatology
  • Virology
  • Molecular Biology

Background:

  • Hepatitis C virus (HCV) proteins are known to activate the unfolded protein response (UPR) in experimental settings.
  • The specific role of the UPR in the liver injury associated with chronic HCV infection remains unclear.
  • This study aimed to elucidate the involvement of the UPR in the pathogenesis of chronic HCV.

Purpose of the Study:

  • To investigate the activation status of the UPR in liver biopsy samples from patients with chronic HCV.
  • To determine the correlation between UPR components and liver injury markers in chronic HCV.

Main Methods:

  • Analysis of liver biopsy samples from 124 patients with chronic HCV and 24 healthy controls.
  • Quantification of hepatic mRNA expression for UPR components using real-time PCR.
  • Assessment of Glucose-regulated protein (GRP) 78 protein levels via immunohistochemistry.

Main Results:

  • Significantly lower mRNA expression of GRP78 and growth arrest and damage inducible protein 34 (GADD34) was observed in HCV patients compared to controls.
  • No significant differences were found in the expression of GRP94, spliced X-box binding protein 1 (sXBP1), C/EBP homologous protein (CHOP), EDEM mRNA, or GRP78 protein.
  • No associations were identified between UPR elements and inflammation or fibrosis in the studied HCV cohort.

Conclusions:

  • Downstream components of the UPR do not appear to be activated in individuals with chronic HCV infection.
  • The UPR may not play a significant role in the liver injury observed in chronic HCV pathogenesis.
Abstract

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