title: The Us2 gene product of herpes simplex virus 2 is a membrane-associated ubiquitin-interacting protein.
abstract: The Us2 gene encodes a tegument protein that is conserved in most members of the Alphaherpesvirinae. Previous studies on the pseudorabies virus (PRV) Us2 ortholog indicated that it is prenylated, associates with membranes, and spatially regulates the enzymatic activity of the MAP (mitogen-activated protein) kinase ERK (extracellular signal-related kinase) through direct binding and sequestration of ERK at the cytoplasmic face of the plasma membrane. Here we present an analysis of the herpes simplex virus 2 (HSV-2) Us2 ortholog and demonstrate that, like PRV Us2, HSV-2 Us2 is a virion component and that, unlike PRV Us2, it does not interact with ERK in yeast two-hybrid assays. HSV-2 Us2 lacks prenylation signals and other canonical membrane-targeting motifs yet is tightly associated with detergent-insoluble membranes and localizes predominantly to recycling endosomes. Experiments to identify cellular proteins that facilitate HSV-2 Us2 membrane association were inconclusive; however, these studies led to the identification of HSV-2 Us2 as a ubiquitin-interacting protein, providing new insight into the functions of HSV-2 Us2.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada.
authors.forename: Ming-Hsi
authors.initials: MH
authors.lastname: Kang
authors.forename: Bibhuti B
authors.initials: BB
authors.lastname: Roy
authors.forename: Renée L
authors.initials: RL
authors.lastname: Finnen
authors.forename: Valerie
authors.initials: V
authors.lastname: Le Sage
authors.forename: Susan M
authors.initials: SM
authors.lastname: Johnston
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Banfield
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D011992:Endosomes / Q000821:virology; D005814:Genes, Viral; D057809:HEK293 Cells; D018258:Herpesvirus 2, Human / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System; D054876:Prenylation; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000502:physiology*
chemical_list: C584391:US2 protein, herpes simplex virus 2; D025801:Ubiquitin; D014759:Viral Envelope Proteins