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

Saisai Chen, Thomas Shenk, Maciej T. Nogalski

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)18971-18982
Number of pages12
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number38
DOIs
StatePublished - Sep 17 2019

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Calcium homeostasis
  • Cell migration
  • Cytomegalovirus
  • Purinergic receptors

Fingerprint Dive into the research topics of 'P2Y2 purinergic receptor modulates virus yield, calcium homeostasis, and cell motility in human cytomegalovirus-infected cells'. Together they form a unique fingerprint.

Cite this