P2Y2 purinergic receptor modulates virus yield, calcium homeostasis, and cell motility in human cytomegalovirus-infected cells.

TitleP2Y2 purinergic receptor modulates virus yield, calcium homeostasis, and cell motility in human cytomegalovirus-infected cells.
Publication TypeJournal Article
Year of Publication2019
AuthorsChen, S, Shenk, T, Nogalski, MT
JournalProc Natl Acad Sci U S A
Volume116
Issue38
Pagination18971-18982
Date Published2019 Sep 17
ISSN1091-6490
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.

DOI10.1073/pnas.1907562116
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID31481624
PubMed Central IDPMC6754545
Grant ListR01 AI112951 / AI / NIAID NIH HHS / United States
R56 AI112951 / AI / NIAID NIH HHS / United States