title: Regulation of Kaposi's sarcoma-associated herpesvirus reactivation by dopamine receptor-mediated signaling pathways.
abstract: BACKGROUND
  Kaposi's sarcoma-associated herpesvirus (KSHV) possesses two distinct life cycles, lytic replication and latency. An immediate early viral protein, Replication and transcription activator (RTA), is responsible for the virus switch from latency to active replication.
  
  
  METHODS
  To identify cellular pathways that reactivate KSHV replication, an RTA-responsive viral early promoter, PAN, coupled with an enhanced green fluorescent protein (EGFP) reporter was delivered into a KSHV latently infected B cell line. Five different chemical libraries with defined cellular targets were screened for their ability to induce the PAN promoter as an indication of lytic replication.
  
  
  RESULTS
  We identified seven chemicals that disrupted latency in KSHV latently infected B cells, five being N-acyl-dopamine derivatives. We showed that these chemicals reactivate KSHV through interacting with dopamine receptors, and that KSHV utilizes dopamine receptors and the associated PKA and MAP kinase pathways to detect and transmit stress signals for reactivation.
  
  
  CONCLUSIONS
  Our study identified two cellular signaling pathways that mediate KSHV reactivation and provided a chemical genetics approach to identify new endogenous activators with therapeutic potential against herpesvirus associated malignancies.
authors.affiliation: School of Dentistry, University of California at Los Angeles, Los Angeles, CA, USA.
authors.forename: Shaoying
authors.initials: S
authors.lastname: Lee
authors.forename: Hongyu
authors.initials: H
authors.lastname: Deng
authors.forename: Fuqu
authors.initials: F
authors.lastname: Yu
authors.forename: William P
authors.initials: WP
authors.lastname: Melega
authors.forename: Robert
authors.initials: R
authors.lastname: Damoiseaux
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Bradley
authors.forename: Ren
authors.initials: R
authors.lastname: Sun
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology*; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D019288:Herpesvirus 8, Human / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014775:Virus Activation; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D011954:Receptors, Dopamine; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D004298:Dopamine