Ganetespib, an HSP90 inhibitor, kills Epstein-Barr virus (EBV)-infected B and T cells and reduces the percentage of EBV-infected cells in the blood.
HSP90 inhibitors have been shown to kill Epstein-Barr virus (EBV)-infected cells by reducing the level of EBV EBNA-1 and/or LMP1. We treated virus-infected cells with ganetespib, an HSP90 inhibitor currently being evaluated in multiple clinical trials for cancer and found that the drug killed EBV-positive B and T cells and reduced the level of both EBV EBNA-1 and LMP1. Treatment of cells with ganetespib also reduced the level of pAkt. Ganetespib delayed the onset of EBV-positive lymphomas and prolonged survival in SCID mice inoculated with one EBV-transformed B-cell line, but not another B-cell line. The former cell line showed lower levels of EBNA-1 after treatment with ganetespib in vitro. Treatment of a patient with T-cell chronic active EBV with ganetespib reduced the percentage of EBV-positive cells in the peripheral blood. These data indicate that HSP90 inhibitors may have a role in the therapy of certain EBV-associated diseases.
a Laboratory of Infectious Diseases , National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda , MD , USA.
Amber
A
Shatzer
a Laboratory of Infectious Diseases , National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda , MD , USA.
Mir A
MA
Ali
a Laboratory of Infectious Diseases , National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda , MD , USA.
Mayra
M
Chavez
a Laboratory of Infectious Diseases , National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda , MD , USA.
Kennichi
K
Dowdell
b Developmental Therapeutics Branch , National Cancer Institute, National Institutes of Health , Bethesda , MD , USA.
Min-Jung
MJ
Lee
b Developmental Therapeutics Branch , National Cancer Institute, National Institutes of Health , Bethesda , MD , USA.
Yusuke
Y
Tomita
c Synta Pharmaceuticals , Lexington , MA , USA.
Iman
I
El-Hariry
b Developmental Therapeutics Branch , National Cancer Institute, National Institutes of Health , Bethesda , MD , USA.
Jane B
JB
Trepel
c Synta Pharmaceuticals , Lexington , MA , USA.
David A
DA
Proia
a Laboratory of Infectious Diseases , National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda , MD , USA.
Jeffrey I
JI
Cohen
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects* / Q000821:virology*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D020031:Epstein-Barr Virus Infections / Q000097:blood* / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics / Q000378:metabolism; D005260:Female; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D018655:Lymphocyte Count; D051379:Mice; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000187:drug effects* / Q000821:virology*; D014230:Triazoles / Q000494:pharmacology*
D019309:Epstein-Barr Virus Nuclear Antigens; D050883:HSC70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C494371:HSPA8 protein, human; C533237:STA 9090; D014230:Triazoles; C417029:EBV-encoded nuclear antigen 1
Burkitt’s lymphoma; Epstein–Barr virus; Ganetespib; HSP90
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