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Activation of NIX-mediated mitophagy by an interferon regulatory factor homologue of human herpesvirus

Author

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  • Mai Tram Vo

    (Johns Hopkins University School of Medicine)

  • Barbara J. Smith

    (Johns Hopkins University School of Medicine)

  • John Nicholas

    (Johns Hopkins University School of Medicine)

  • Young Bong Choi

    (Johns Hopkins University School of Medicine)

Abstract

Viral control of mitochondrial quality and content has emerged as an important mechanism for counteracting the host response to virus infection. Despite the knowledge of this crucial function of some viruses, little is known about how herpesviruses regulate mitochondrial homeostasis during infection. Human herpesvirus 8 (HHV-8) is an oncogenic virus causally related to AIDS-associated malignancies. Here, we show that HHV-8-encoded viral interferon regulatory factor 1 (vIRF-1) promotes mitochondrial clearance by activating mitophagy to support virus replication. Genetic interference with vIRF-1 expression or targeting to the mitochondria inhibits HHV-8 replication-induced mitophagy and leads to an accumulation of mitochondria. Moreover, vIRF-1 binds directly to a mitophagy receptor, NIX, on the mitochondria and activates NIX-mediated mitophagy to promote mitochondrial clearance. Genetic and pharmacological interruption of vIRF-1/NIX-activated mitophagy inhibits HHV-8 productive replication. Our findings uncover an essential role of vIRF-1 in mitophagy activation and promotion of HHV-8 lytic replication via this mechanism.

Suggested Citation

  • Mai Tram Vo & Barbara J. Smith & John Nicholas & Young Bong Choi, 2019. "Activation of NIX-mediated mitophagy by an interferon regulatory factor homologue of human herpesvirus," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11164-2
    DOI: 10.1038/s41467-019-11164-2
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    Cited by:

    1. Yiqi Huang & Valter Bergant & Vincent Grass & Quirin Emslander & M. Sabri Hamad & Philipp Hubel & Julia Mergner & Antonio Piras & Karsten Krey & Alexander Henrici & Rupert Öllinger & Yonas M. Tesfamar, 2024. "Multi-omics characterization of the monkeypox virus infection," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Qin Yan & Jing Zhou & Ziyu Wang & Xiangya Ding & Xinyue Ma & Wan Li & Xuemei Jia & Shou-Jiang Gao & Chun Lu, 2023. "NAT10-dependent N4‐acetylcytidine modification mediates PAN RNA stability, KSHV reactivation, and IFI16-related inflammasome activation," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    3. Dongqi Nan & Chenglong Rao & Zhiheng Tang & Wenbo Yang & Pan Wu & Jiangao Chen & Yupei Xia & Jingmin Yan & Wenzheng Liu & Ziyuan Zhang & Zhiqiang Hu & Hai Chen & Yaling Liao & Xuhu Mao & Xiaoyun Liu &, 2024. "Burkholderia pseudomallei BipD modulates host mitophagy to evade killing," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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