Human cytomegalovirus pUL37x1-induced calcium flux activates PKCα, inducing altered cell shape and accumulation of cytoplasmic vesicles

Ronit Sharon-Friling, Thomas Shenk

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The human cytomegalovirus immediate-early protein pUL37x1 induces the release of Ca2+ 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 Ca2+-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.

Original languageEnglish (US)
Pages (from-to)E1140-E1148
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number12
DOIs
StatePublished - Mar 25 2014

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Capsid envelopment
  • Virion assembly
  • Virus-induced membranes

Fingerprint Dive into the research topics of 'Human cytomegalovirus pUL37x1-induced calcium flux activates PKCα, inducing altered cell shape and accumulation of cytoplasmic vesicles'. Together they form a unique fingerprint.

  • Cite this