title: Human cytomegalovirus pUL37x1-induced calcium flux activates PKCα, inducing altered cell shape and accumulation of cytoplasmic vesicles.
abstract: The human cytomegalovirus immediate-early protein pUL37x1 induces the release of Ca(2+) stores from the endoplasmic reticulum into the cytosol. This release causes reorganization of the cellular actin cytoskeleton with concomitant cell rounding. Here we demonstrate that pUL37x1 activates Ca(2+)-dependent protein kinase Cα (PKCα). Both PKCα and Rho-associated protein kinases are required for actin reorganization and cell rounding; however, only PKCα is required for the efficient production of virus progeny, arguing that HCMV depends on the kinase for a second function. PKCα activation is also needed for the production of large (1-5 μm) cytoplasmic vesicles late after infection. The production of these vesicles is blocked by inhibition of fatty acid or phosphatidylinositol-3-phosphate biosynthesis, and the failure to produce vesicles is correlated with substantially reduced production of enveloped virus capsids. These results connect earlier work identifying a requirement for lipid synthesis with specific morphological changes, and support the argument that the PKCα-induced large vesicles are either required for the efficient production of mature virus particles or serve as a marker for the process.
authors.affiliation: Department of Molecular Biology, Princeton University, Princeton, NJ 08544.
authors.forename: Ronit
authors.initials: R
authors.lastname: Sharon-Friling
authors.forename: Thomas
authors.initials: T
authors.lastname: Shenk
mesh_terms: D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D048430:Cell Shape; D003593:Cytoplasm / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation; D017874:Immediate-Early Proteins / Q000502:physiology*; D017136:Ion Transport; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D017874:Immediate-Early Proteins; D034741:RNA, Small Interfering; C420323:UL37 protein, Human herpesvirus 5; D051571:Protein Kinase C-alpha; D002118:Calcium
keywords: capsid envelopment; virion assembly; virus-induced membranes