The antiapoptotic herpes simplex virus glycoprotein J localizes to multiple cellular organelles and induces reactive oxygen species formation.
The Us5 gene of herpes simplex virus (HSV) encodes glycoprotein J (gJ). The only previously reported function of gJ was its ability to inhibit apoptosis. However, the mechanism by which gJ prevents apoptosis is not understood, and it is not known whether gJ mediates additional cellular effects. In this study, we evaluated the expression, localization, and cellular effects of Us5/gJ. Us5 was first expressed 4 h after infection. gJ was detectable at 6 h and was expressed in glycosylated and unglycosylated forms. Us5 was regulated as a late gene, with partial dependency on DNA replication for expression. Us5 expression was delayed in the absence of ICP22; furthermore, expression of Us5 in trans protected cells from apoptosis induced by an HSV mutant with deletion of ICP27, suggesting that the antiapoptotic effects of ICP22 and ICP27 are mediated in part through effects on gJ expression. Within HSV-infected or Us5-transfected cells, gJ was distributed widely, especially to the endoplasmic reticulum, trans-Golgi network, and early endosomes. gJ interacted with F(o)F(1) ATP synthase subunit 6 by a yeast two-hybrid screen and had strong antiapoptotic effects, which were mediated by protein rather than mRNA. Antiapoptotic activity required the extracellular and transmembrane domains of gJ, but not the intracellular domain. Consistent with inhibition of F(o)F(1) ATP synthase function, Us5 was required for HSV-induced reactive oxygen species (ROS) formation, and gJ was sufficient to induce ROS in Us5-transfected cells. Thus, HSV gJ is a multifunctional protein, modulating other cellular processes in addition to inhibition of apoptosis.
Aubert
Martine
M
Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195, USA.
Chen
Zheng
Z
Lang
Robin
R
Dang
Chung H
CH
Fowler
Carla
C
Sloan
Derek D
DD
Jerome
Keith R
KR
D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral; D006031:Glycosylation; D006801:Humans; D015388:Organelles / Q000737:chemistry*; D011485:Protein Binding; D006180:Proton-Translocating ATPases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018139:Simplexvirus / Q000276:immunology*; D013997:Time Factors; D020798:Two-Hybrid System Techniques; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
D017382:Reactive Oxygen Species; D014759:Viral Envelope Proteins; C077970:glycoprotein J, herpesvirus simiae; D006180:Proton-Translocating ATPases