DOI: 10.1101/506113Dec 25, 2018Paper

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

BioRxiv : the Preprint Server for Biology
Mai Tram VoYoung Bong Choi

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 found 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. In short, our findings uncover an essential role of vIRF-1 in mitophagy activation for successful lytic replication of HHV-8.

Related Concepts

Acquired Immunodeficiency Syndrome
Malignant Neoplasms
Herpesviridae
Lysis
Mitochondria
Oncogenic Viruses
Virus Diseases
Virus Replication
Virus
Human herpes simplex virus

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