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| Content Provider | PubMed Central |
|---|---|
| Author | Sun, Xiaoping Barlow, Elizabeth A. Ma, Shidong Hagemeier, Stacy R. Duellman, Sarah J. Burgess, Richard R. Judy, Tellam Khanna, Rajiv Kenney, Shannon C. |
| Abstract | EBV causes infectious mononucleosis and is associated with certain malignancies. EBV nuclear antigen 1 (EBNA1) mediates EBV genome replication, partition, and transcription, and is essential for persistence of the viral genome in host cells. Here we demonstrate that Hsp90 inhibitors decrease EBNA1 expression and translation, and that this effect requires the Gly-Ala repeat domain of EBNA1. Hsp90 inhibitors induce the death of established, EBV-transformed lymphoblastoid cell lines at doses nontoxic to normal cells, and this effect is substantially reversed when lymphoblastoid cell lines are stably infected with a retrovirus expressing a functional EBNA1 mutant lacking the Gly-Ala repeats. Hsp90 inhibitors prevent EBV transformation of primary B cells, and strongly inhibit the growth of EBV-induced lymphoproliferative disease in SCID mice. These results suggest that Hsp90 inhibitors may be particularly effective for treating EBV-induced diseases requiring the continued presence of the viral genome. |
| Related Links | http://dx.doi.org/10.1073/pnas.0910717107 |
| Ending Page | 3151 |
| Page Count | 6 |
| Starting Page | 3146 |
| File Format | |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 7 |
| Volume Number | 107 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2010-02-16 |
| Access Restriction | Open |
| Rights Holder | National Academy of Sciences |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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