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

Mai Tram Vo, Barbara J. Smith, John Nicholas, Young Choi

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number3203
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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Mitochondrial Degradation
Interferon Regulatory Factors
interferon
Herpesviridae
Human Herpesvirus 8
viruses
Chemical activation
Mitochondria
activation
mitochondria
Viruses
clearances
infectious diseases
Oncogenic viruses
acquired immunodeficiency syndrome
homeostasis
interruption
promotion
Oncogenic Viruses
Virus Diseases

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Activation of NIX-mediated mitophagy by an interferon regulatory factor homologue of human herpesvirus. / Vo, Mai Tram; Smith, Barbara J.; Nicholas, John; Choi, Young.

In: Nature communications, Vol. 10, No. 1, 3203, 01.12.2019.

Research output: Contribution to journalArticle

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