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

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.

SUBMITTER: Vo MT

PROVIDER: S-EPMC6642096 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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

Vo Mai Tram MT Smith Barbara J BJ Nicholas John J Choi Young Bong YB

Nature communications 20190719 1

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 mitochondr ...[more]

PMID: 31324791

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Dataset Information

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

Publications

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

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