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Mitochondria Redistribution in Enterovirus A71 Infected Cells and Its Effect on Virus Replication

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Virologica Sinica

Abstract

Enterovirus A71 (EV-A71) is one of the main causative agents of hand, foot and mouth disease (HFMD) and it also causes severe neurologic complications in infected children. The interactions between some viruses and the host mitochondria are crucial for virus replication and pathogenicity. In this study, it was observed that EV-A71 infection resulted in a perinuclear redistribution of the mitochondria. The mitochondria rearrangement was found to require the microtubule network, the dynein complex and a low cytosolic calcium concentration. Subsequently, the EV-A71 non-structural protein 2BC was identified as the viral protein capable of inducing mitochondria clustering. The protein was found localized on mitochondria and interacted with the mitochondrial Rho GTPase 1 (RHOT1) that is a key protein required for attachment between the mitochondria and the motor proteins, which are responsible for the control of mitochondria movement. Additionally, suppressing mitochondria clustering by treating cells with nocodazole, EHNA, thapsigargin or A23187 consistently inhibited EV-A71 replication, indicating that mitochondria recruitment played a crucial role in the EV-A71 life cycle. This study identified a novel function of the EV-A71 2BC protein and provided a potential model for the regulation of mitochondrial motility in EV-A71 infection.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (NSFC) (Grants Nos. 81621091, 31370201). We are grateful to Prof. Paul Chu, Guest Professor of the Institute of Microbiology, Chinese Academy of Sciences (CAS), for his help during the preparation of the manuscript. We thank Xiaolan Zhang and Tong Zhao, Institute of Microbiology, CAS, for technical help with confocal microscopy and flow cytometry. We also thank Fulian Liao and Weihua Zhuang for their assistance with the experiments.

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  1. Yang Yang and Haolong Cong have contributed equally to this study.

Authors and Affiliations

  1. Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China

    Yang Yang, Haolong Cong, Lei Song, Wenliang Zhang, Chunrui Li & Po Tien

  2. University of the Chinese Academy of Sciences, Beijing, 100101, China

    Yang Yang, Chunrui Li & Po Tien

  3. Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, China

    Ning Du

  4. College of Life Sciences, Inner Mongolia Agriculture University, Hohhot, 010018, China

    Xiaodong Han

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  1. Yang Yang
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  2. Haolong Cong
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  3. Ning Du
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  5. Lei Song
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Contributions

YY, HC and PT designed the research. YY and HC performed the experiments. ND, XH, LS, WZ and CL provided experiment support. YY and HC wrote the manuscript. All authors have read and approved the final manuscript for submission.

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Correspondence to Po Tien.

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

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Yang, Y., Cong, H., Du, N. et al. Mitochondria Redistribution in Enterovirus A71 Infected Cells and Its Effect on Virus Replication. Virol. Sin. 34, 397–411 (2019). https://doi.org/10.1007/s12250-019-00120-5

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