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Updated: Jul 3, 2026

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Alphavirus M1 disrupts super-enhancer-driven oncogenic transcription via non-structural protein NSP2 in osteosarcoma

Jiajun Zhang1,2, Lifeng Yin1,2, Qianqian Han3

  • 1Department of Musculoskeletal Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.

Nature Communications
|July 1, 2026
PubMed

Insights

This study shows that the M1 alphavirus effectively targets osteosarcoma (OS) cells, offering a new avenue for cancer therapy. The virus works by degrading a key protein, RPB1, essential for cancer cell growth.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Oncolytic virotherapy shows potential against various cancers.
  • Osteosarcoma (OS) remains an underexplored area for virotherapy applications.

Purpose of the Study:

  • To investigate the oncolytic activity of the M1 alphavirus against osteosarcoma.
  • To elucidate the underlying molecular mechanisms of M1's anti-tumor effects in OS.

Main Methods:

  • Cell culture and infection with M1 alphavirus.
  • Proteomic analysis and Chromatin Immunoprecipitation sequencing (ChIP-seq).
  • Investigation of viral protein interactions and ubiquitination pathways.

Main Results:

  • M1 virus exhibits significant oncolytic activity against OS cells.
  • M1 infection targets the DNA-directed RNA polymerase II subunit RPB1, crucial for super-enhancer activity.
  • Viral protein NSP2 disrupts super-enhancer activity by degrading RPB1 via a specific protein complex.

Conclusions:

  • M1 alphavirus demonstrates potent oncolytic activity in osteosarcoma.
  • A novel mechanism involving RPB1 degradation by M1 is identified.
  • RPB1 is proposed as a potential biomarker for predicting response to M1 virotherapy in OS.

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