期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2014
卷号：111
期号：12
页码：E1140-E1148
DOI：10.1073/pnas.1402515111
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 C (PKC). Both PKC and Rho-associated protein kinases are required for actin reorganization and cell rounding; however, only PKC is required for the efficient production of virus progeny, arguing that HCMV depends on the kinase for a second function. PKC activation is also needed for the production of large (1-5 m) 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 PKC-induced large vesicles are either required for the efficient production of mature virus particles or serve as a marker for the process.
