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Rational strategies for designing next-generation oncolytic viruses based on transcriptome analysis of tumor cells

Naeme Javid1, Shahriyar Abdoli2, Majid Shahbazi3,4

  • 1Department of Molecular Medicine, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran.

Frontiers in Oncology
|January 24, 2025
PubMed
Abstract

Insights

Oncolytic herpes simplex viruses (oHSVs) target cancer cells. This study analyzed gene expression changes in oHSV-1 infected cells, identifying proteasome pathway alterations and key genes like GADD45g for potential therapeutic strategies.

Area of Science:

  • Oncology
  • Virology
  • Genomics
  • Systems Biology

Background:

  • Oncolytic herpes simplex viruses (oHSVs) are promising biotherapeutics for cancer treatment, selectively targeting and destroying tumor cells.
  • Understanding the host cell's genomic and metabolic response to oHSV infection is crucial for optimizing their therapeutic efficacy.

Purpose of the Study:

  • To investigate the functional genomic and metabolic pathway alterations in human cancer cells upon infection with oHSV-1.
  • To identify key genes and pathways influenced by oHSV-1 infection that modulate the virus-cancer cell interaction.
  • To explore the potential of transcriptome changes for predicting oncolytic virus efficacy.

Main Methods:

  • Utilized two gene expression datasets from the Gene Expression Omnibus (GEO) database for tumor cells infected with oHSV-1 (G207) and control cells.
  • Processed and normalized data using R software, identifying common differentially expressed genes and hub genes.
  • Validated hub gene expression using real-time quantitative polymerase chain reaction (qRT-PCR) in MDA-MB-231 breast cancer cells.

Main Results:

  • Significant alterations in proteasome pathway-related genes were observed between infected and non-infected cells, with the proteasome-mediated ubiquitin-dependent protein catabolic process identified as a key biological pathway (p-value: 5.8E-21).
  • Extracellular exosomes and protein binding were identified as significant cellular components and molecular functions, respectively.
  • Key hub genes including PSMD2, PSMD4, PSMA2, and GADD45g were identified, with GADD45g showing potential in oncolytic HSV-1 proliferation.

Conclusions:

  • Transcriptome analysis reveals significant host cell responses to oHSV-1 infection, particularly involving the proteasome pathway.
  • Identified hub genes and pathways provide insights into the virus-cancer cell dynamics.
  • These findings can inform the development of next-generation oncolytic viruses and predict their therapeutic efficacy.
Keywords:
GADD45gHSV-1hub geneoncolytictranscriptome

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