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STAT3 signaling pathway plays importantly genetic and functional roles in HCV infection

Yuzhu Song1,2, Xianyao Yang1, Yunsong Shen2

  • 1Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China.

Molecular Genetics & Genomic Medicine
|June 21, 2019
PubMed

Insights

Genetic variations in the Signal Transducers and Activators of Transcription 3 (STAT3) pathway influence Hepatitis C virus (HCV) infection risk and patient biochemical features. This study reveals key genetic associations and functional roles of the STAT3 pathway in HCV infection.

Area of Science:

  • Genetics
  • Virology
  • Immunology

Background:

  • Hepatitis C virus (HCV) infection poses a significant global health challenge, leading to severe liver diseases.
  • Host genetic factors are known to influence HCV infection outcomes, including disease progression and treatment response.
  • The Signal Transducers and Activators of Transcription 3 (STAT3) signaling pathway is implicated in HCV infection, yet its genetic associations remain largely unexplored.

Purpose of the Study:

  • To investigate the genetic associations between single nucleotide polymorphisms (SNPs) in the STAT3 signaling pathway and HCV infection.
  • To explore the functional role of the STAT3 signaling pathway in HCV infection through gene expression analysis.

Main Methods:

  • Genotyping of 25 SNPs across six genes (IL6, IL6R, HNF1A, HNF4A, STAT3, ABCC2) in 394 HCV patients and 395 healthy controls.
  • Analysis of gene expression levels in HCV-infected cells, with and without Interleukin 6 (IL6) transfection.

Main Results:

  • Specific SNPs in IL6R (rs4075015, rs7553796) and HNF4A (rs3212172) were significantly associated with HCV infection risk.
  • STAT3 (rs1053023) and IL6R (rs4845617) genotypes correlated with specific biochemical markers (GGT, HDL-C) in HCV patients.
  • IL6 transfection demonstrated a suppressive effect on HCV proliferation in cell-based assays.
  • HCV infection led to increased RNA and protein levels of IL6R, HNF1A, STAT3, and ABCC2.

Conclusions:

  • The STAT3 signaling pathway plays a significant role in modulating HCV infection susceptibility and influencing the biochemical characteristics of infected individuals.
  • Genetic variations within the STAT3 pathway contribute to the complex interplay between host genetics and HCV pathogenesis.
  • Functional evidence supports the involvement of the STAT3 pathway in regulating viral load and host response during HCV infection.
Abstract

Keywords:
HCVSTAT3 signaling pathwaybiochemical characteristicsfunctionalgenetic

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