title: Human cytomegalovirus gH stability and trafficking are regulated by ER-associated degradation and transmembrane architecture.
abstract: The prototypic betaherpesvirus human cytomegalovirus (CMV) establishes life-long persistence within its human host. While benign in healthy individuals, CMV poses a significant threat to the immune compromised, including transplant recipients and neonates. The CMV glycoprotein complex gH/gL/gO mediates infection of fibroblasts, and together with the gH/gL/UL128/130/131 a pentameric complex permits infection of epithelial, endothethial, and myeloid cells. Given the central role of the gH/gL complex during infection, we were interested in studying cellular trafficking of the gH/gL complex through generation of human cells that stably express gH and gL. When expressed alone, CMV gH and gL were degraded through the ER-associated degradation (ERAD) pathway. However, co-expression of these proteins stabilized the polypeptides and enhanced their cell-surface expression. To further define regulatory factors involved in gH/gL trafficking, a CMV gH chimera in which the gH transmembrane and cytoplasmic tail were replaced with that of human CD4 protein permitted cell surface gH expression in absence of gL. We thus demonstrate the ability of distinct cellular processes to regulate the trafficking of viral glycoproteins. Collectively, the data provide insight into the processing and trafficking requirements of CMV envelope protein complexes and provide an example of the co-opting of cellular processes by CMV.
authors.affiliation: Icahn School of Medicine at Mount Sinai, Department of Microbiology, New York, NY 10029, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Gardner
authors.affiliation: Icahn School of Medicine at Mount Sinai, Department of Microbiology, New York, NY 10029, USA.
authors.forename: Rosmel E
authors.initials: RE
authors.lastname: Hernandez
authors.affiliation: Icahn School of Medicine at Mount Sinai, Department of Microbiology, New York, NY 10029, USA.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Noriega
authors.affiliation: Icahn School of Medicine at Mount Sinai, Department of Microbiology, New York, NY 10029, USA.
authors.forename: Domenico
authors.initials: D
authors.lastname: Tortorella
mesh_terms: D002460:Cell Line; D003587:Cytomegalovirus / Q000502:physiology*; D060746:Endoplasmic Reticulum-Associated Degradation; D015870:Gene Expression; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D053586:Virus Internalization
chemical_list: D014759:Viral Envelope Proteins; C071440:glycoprotein H, Cytomegalovirus; D046988:Proteasome Endopeptidase Complex