Affiliation:
1. Department of Laboratory Medicine, University of Washington, Seattle, Washington 98195, and Program in Infectious Diseases and the Vaccine and Infectious Diseases Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109
Abstract
ABSTRACT
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.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Cited by
38 articles.
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