Related Experiment Video

Updated: Jul 25, 2025

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy
08:51

Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy

Published on: April 3, 2018

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PKR-NF-κB Pathway Upstream of IFN-β Induction Is Dysregulated in Oncolytic Sindbis Virus-infected HeLa Cells

Xue Ma1, Tomoko Ogawa1, Zheng Tian1

  • 1Department of Molecular Virology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Anticancer Research
|June 23, 2023
PubMed
Abstract

Insights

Sindbis virus (SINV) effectively infects cancer cells, causing apoptosis. Dysregulation of protein kinase R (PKR) in cancer cells determines the oncolytic effect of SINV, making it a promising cancer therapy.

Area of Science:

  • Virology
  • Cancer Biology
  • Immunology

Background:

  • Sindbis virus (SINV) is a naturally occurring oncolytic virus with selective toxicity towards cancer cells.
  • Recombinant SINV expressing fluorescent proteins enables precise analysis of viral infection and replication dynamics.

Purpose of the Study:

  • To precisely analyze the infection and replication of a recombinant Sindbis virus (SINV) in both cancerous and normal cells.
  • To investigate the antiviral responses in cancer cells versus normal cells upon SINV infection.

Main Methods:

  • Analysis of antiviral responses, including Interferon-beta (IFN-β) mRNA, protein kinase R (PKR), Nuclear Factor-kappa B (NF-κB), and caspase 3/7.
  • Comparative study of SINV infection in cancerous HeLa cells and normal human fibroblast TIG-1-20 cells.

Main Results:

  • SINV infected, replicated, and proliferated in both HeLa and TIG-1-20 cells, but caused lytic infection and apoptosis exclusively in HeLa cells.
  • IFN-β mRNA expression was suppressed in SINV-infected HeLa cells compared to TIG-1-20 cells.
  • Compromised PKR and NF-κB pathway activation in early infection of HeLa cells correlated with suppressed IFN induction.

Conclusions:

  • The dysregulation of protein kinase R (PKR) in HeLa cells is the key determinant for Sindbis virus (SINV) oncolysis.
  • SINV demonstrates potential as an oncolytic agent due to its preferential replication and induction of apoptosis in cancer cells.
Keywords:
IFN-βNF-BPKRSindbis virusoncolytic

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