@article{6dda9acb3aa74b079465396eced2cb2c,
title = "P2Y2 purinergic receptor modulates virus yield, calcium homeostasis, and cell motility in human cytomegalovirus-infected cells",
abstract = "Human cytomegalovirus (HCMV) manipulates many aspects of host cell biology to create an intracellular milieu optimally supportive of its replication and spread. Our study reveals that levels of several components of the purinergic signaling system, including the P2Y2 and P2X5 receptors, are elevated in HCMV-infected fibroblasts. Knockdown and drug treatment experiments demonstrated that P2Y2 enhances the yield of virus, whereas P2X5 reduces HCMV production. The HCMV IE1 protein induces P2Y2 expression; and P2Y2-mediated signaling is important for efficient HCMV gene expression, DNA synthesis, and the production of infectious HCMV progeny. P2Y2 cooperates with the viral UL37x1 protein to regulate cystolic Ca2+ levels. P2Y2 also regulates PI3K/Akt signaling and infected cell motility. Thus, P2Y2 functions at multiple points within the viral replication cycle to support the efficient production of HCMV progeny, and it may facilitate in vivo viral spread through its role in cell migration.",
keywords = "Calcium homeostasis, Cell migration, Cytomegalovirus, Purinergic receptors",
author = "Saisai Chen and Thomas Shenk and Nogalski, {Maciej T.}",
note = "Funding Information: ACKNOWLEDGMENTS. We thank A. Oberstein (University of Illinois) for creating IE1-, IE2-, and IE1/IE2-expressing cells; J. Purdy (University of Arizona) for creating UL37x1-expressing cells; R. Leach and L. Parsons (Princeton University) for computing assistance; G. Leavsky (Princeton University) for assistance with confocal imaging; and members of the T.S. laboratory for scientific discussions. This work was supported by National Institutes of Health Grant AI112951. M.T.N. was supported by American Cancer Society Fellowship PF-14-116-01-MPC. Funding Information: We thank A. Oberstein (University of Illinois) for creating IE1-, IE2-, and IE1/IE2-expressing cells; J. Purdy (University of Arizona) for creating UL37x1-expressing cells; R. Leach and L. Parsons (Princeton University) for computing assistance; G. Leavsky (Princeton University) for assistance with confocal imaging; and members of the T.S. laboratory for scientific discussions. This work was supported by National Institutes of Health Grant AI112951. M.T.N. was supported by American Cancer Society Fellowship PF-14-116-01-MPC. Publisher Copyright: {\textcopyright} 2019 National Academy of Sciences. All rights reserved.",
year = "2019",
month = sep,
day = "17",
doi = "10.1073/pnas.1907562116",
language = "American English",
volume = "116",
pages = "18971--18982",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "38",
}