RT Journal Article
SR Electronic
T1 Activation of NIX-mediated mitophagy and replication by an interferon regulatory factor homologue of human herpesvirus
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 506113
DO 10.1101/506113
A1 Mai Tram Vo
A1 Barbara J Smith
A1 John Nicholas
A1 Young Bong Choi
YR 2018
UL http://biorxiv.org/content/early/2018/12/25/506113.abstract
AB 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.