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
| Autor: | Yusuke Tomita, Mir A. Ali, Jeffrey I. Cohen, Min-Jung Lee, Amber N. Shatzer, Mayra Chavez, Jane B. Trepel, David A. Proia, Iman El-Hariry, Kennichi C. Dowdell |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Epstein-Barr Virus Infections Herpesvirus 4 Human Cell Survival T-Lymphocytes Ganetespib Mice SCID Biology medicine.disease_cause Virus Article Hsp90 inhibitor 03 medical and health sciences Mice 0302 clinical medicine hemic and lymphatic diseases medicine Animals Humans HSP90 Heat-Shock Proteins Lymphocyte Count Cells Cultured Cell Line Transformed B-Lymphocytes HSC70 Heat-Shock Proteins Cancer Hematology Triazoles medicine.disease Virology Epstein–Barr virus In vitro Disease Models Animal 030104 developmental biology Oncology Epstein-Barr Virus Nuclear Antigens Cell culture 030220 oncology & carcinogenesis Female Burkitt's lymphoma |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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