Targeting of mTOR catalytic site inhibits multiple steps of the HIV-1 lifecycle and suppresses HIV-1 viremia in humanized mice
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- Alonso Heredia
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201;
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- Nhut Le
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201;
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- Ronald B. Gartenhaus
- Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201
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- Edward Sausville
- Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201
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- Sandra Medina-Moreno
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201;
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- Juan C. Zapata
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201;
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- Charles Davis
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201;
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- Robert C. Gallo
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201;
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- Robert R. Redfield
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201;
書誌事項
- 公開日
- 2015-07-13
- DOI
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- 10.1073/pnas.1511144112
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:title>Significance</jats:title> <jats:p>Most HIV antiretrovirals target viral proteins. Unfortunately, HIV mutates under drug pressure, which can lead to drug resistance. Targeting cellular proteins that HIV necessitates in its lifecycle may help overcome HIV drug resistance because cellular proteins have lower mutations rates than do HIV proteins. Mammalian target of rapamycin (mTOR) is a cellular kinase that forms two complexes (mTORC-1 and -2), regulating protein translation and transduction signaling. We demonstrate that dual targeting of mTORC-1/2 with the catalytic inhibitor INK128 blocks HIV by interfering with entry and with transcription (basal and induced). Importantly, INK128 suppressed HIV in a preclinical animal model, suggesting that mTORC-1/2 catalytic inhibitors may help control HIV in patients, particularly in those with drug-resistant HIV.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 112 (30), 9412-9417, 2015-07-13
Proceedings of the National Academy of Sciences