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Visualization of the Oncolytic Alphavirus M1 Life Cycle in Cancer Cells

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Virologica Sinica

A Correction to this article was published on 15 July 2021

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Abstract

Oncolytic alphavirus M1 has been shown to selectively target and kill cancer cells, but cytopathic morphologies induced by M1 virus and the life cycle of the M1 strain in cancer cells remain unclear. Here, we study the key stages of M1 virus infection and replication in the M1 virus-sensitive HepG2 liver cancer cell line by transmission electron microscopy, specifically examining viral entry, assembly, maturation and release. We found that M1 virus induces vacuolization of cancer cells during infection and ultimately nuclear marginalization, a typical indicator of apoptosis. Specifically, our results suggest that the endoplasmic reticulum participates in the assembly of nucleocapsids. In the early and late stage of infection, three kinds of special cytopathic vacuoles are formed and appear to be involved in the replication, maturation and release of the virus. Taken together, our data displayed the process of M1 virus infection of tumor cells and provide the structural basis for the study of M1 virus-host interactions.

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Acknowledgements

This research was supported by the Science and Technology Program of Guangzhou (201707020003), the Pioneering Talents Project of Guangzhou Development Zone, Guangdong Province (CY2018-012), the Guangzhou People's Livelihood Science and Technology Tackling Key Project (201803010113), the Young Teacher Training Program of Sun Yat-sen University (20ykpy22), and the National Natural Science Foundation of China (No. 81802536).

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Author notes

  1. Jia Dan and Lin Nie contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China

    Jia Dan, Cuiying Xu, Jing Cai, Yuan Lin, Jun Hu, Wenbo Zhu, Guangmei Yan & Jiankai Liang

  2. State Key Lab for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, China

    Lin Nie, Xudong Jia, Yinyin Li, Dong Chen & Qinfen Zhang

  3. Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China

    Ying Liu

  4. Department of Urology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China

    Cheng Hu

Authors
  1. Jia Dan
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  2. Lin Nie
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Contributions

JD contributed to the experimental design and cellular experiments. JD and LN contributed to the EM observations, data analyses, manuscript writing and editing. XJ contributed to the 2D classification. JC, YL, JL, JH, GY and WZ contributed to the operations at the TEM facilities. YL and DC contributed to TEM sample preparation. CX, YL and CH contributed to the data analyses. JL and QZ contributed to the manuscript revisions. QZ contributed to the EM observations, data analyses, and project supervision.

Corresponding authors

Correspondence to Jiankai Liang or Qinfen Zhang.

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The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

The original online version of this article was revised: In the original version of Fig. 6, the names of image panels (row 2 to row 5) were mislabeled during figure layout.

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Dan, J., Nie, L., Jia, X. et al. Visualization of the Oncolytic Alphavirus M1 Life Cycle in Cancer Cells. Virol. Sin. 36, 655–666 (2021). https://doi.org/10.1007/s12250-020-00339-7

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  • DOI: https://doi.org/10.1007/s12250-020-00339-7

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