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Cellular resistance to an oncolytic virus is driven by chronic activation of innate immunity

Alejandra Larrieux1, Rafael Sanjuán1

  • 1Institute for Integrative Systems Biology (I2SysBio), Universitat de València-CSIC, Paterna, València 46980, Spain.

Iscience
|January 2, 2023
PubMed

Insights

Cellular resistance to oncolytic viruses can hinder cancer virotherapy. Researchers identified conserved gene expression changes, including interferon-stimulated genes, conferring cross-resistance to viruses in melanoma and colon carcinoma cells.

Area of Science:

  • Oncology
  • Virology
  • Immunology

Background:

  • Cellular resistance to oncolytic viruses is a significant challenge for cancer virotherapy.
  • Understanding resistance mechanisms is crucial for improving treatment efficacy.

Purpose of the Study:

  • To investigate the mechanisms of cellular resistance to oncolytic vesicular stomatitis virus (VSV-D51) in cancer cells.
  • To identify genetic factors and pathways involved in acquired viral resistance.

Main Methods:

  • Isolation and characterization of resistant B16 mouse melanoma cell lines.
  • RNA sequencing (RNA-seq) to analyze global gene expression changes.
  • Assessment of cross-resistance to different viruses.

Main Results:

  • Resistant cells exhibited broad gene expression changes, notably chronic upregulation of interferon-stimulated genes.
  • Activated innate immunity in resistant cells conferred cross-resistance to VSV and Sindbis virus.
  • Identified novel differentially expressed genes (Mnda, Psmb8, Btn2a2) potentially involved in antiviral response.
  • Observed conserved transcriptomic changes in B16 and CT26 cell lines, suggesting predictable resistance mechanisms.

Conclusions:

  • Cellular resistance to oncolytic viruses involves conserved genetic mechanisms, potentially predictable.
  • Upregulation of interferon-stimulated genes and innate immunity activation are key features of resistance.
  • Further research into identified genes may reveal novel antiviral functions and therapeutic targets.
Keywords:
ImmunologyMolecular physiologyVirology

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