A peptide-based inhibitor for prevention of B cell hyperproliferation induced by Epstein-Barr virus.
Epstein-Barr virus (EBV) infects and transforms resting B lymphocytes in vitro. The virus can also cause B cell lymphomas in immunosuppressed humans. Indeed, EBV-mediated post-transplant lymphoproliferative disease causes significant complications in transplant recipients, including loss of the transplanted organ and even death. The limited treatment options include, nonspecific targeting of B cell surface antigens with monoclonal antibodies or withdrawal of immunosuppression. These therapies fail in approximately 50% of patients. Clearly, treatments that specifically target EBV-infected cells are desirable. The EBV antigen EBNA3C regulates cell cycle by targeting critical cellular complexes such as cyclin A/cdk2, SCF(Skp2), and Rb. Here, we use a 20-amino-acid EBNA3C-derived peptide, fused to an HIV TAT tag for efficient delivery, to disrupt cell cycle regulation by EBNA3C. The peptide inhibited hyperproliferation of EBV-infected B cell lines and reduced in vitro immortalization of primary B lymphocytes by EBV. Importantly, the peptide inhibited lymphoblastoid outgrowth from the blood of an EBV-positive transplant patient in vitro.
Knight
Jason S
JS
Department of Microbiology, University of Pennsylvania Medical School, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104, USA.
Lan
Ke
K
Bajaj
Bharat
B
Sharma
Nikhil
N
Tsai
Donald E
DE
Robertson
Erle S
ES
D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000821:virology*; D049109:Cell Proliferation / Q000187:drug effects*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D019309:Epstein-Barr Virus Nuclear Antigens; D005260:Female; D015696:Gene Products, tat / Q000235:genetics / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology; D004854:Herpesvirus 4, Human / Q000472:pathogenicity*; D006801:Humans; D016030:Kidney Transplantation; D008223:Lymphoma / Q000473:pathology / Q000821:virology; D010446:Peptide Fragments / Q000493:pharmacokinetics / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology
D000956:Antigens, Viral; C498774:EBNA-3C, epstein-barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D015696:Gene Products, tat; D006131:Growth Inhibitors; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins