control of kaposis sarcoma-associated herpesvirus reactivation induced by multiple signals控制卡波济氏肉瘤相关疱疹病毒再活化诱导由多个信号.pdf

Control of Kaposi’s Sarcoma-Associated Herpesvirus Reactivation Induced by Multiple Signals 1.¤ 1,2. 1 1 1 2 Fuqu Yu , Ibrahim Al-Shyoukh , Jiaying Feng , Xudong Li , Chia Wei Liao , Chih-Ming Ho , Jeff S. 3 1 Shamma , Ren Sun * 1 Department of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, California, United States of America, 2 Mechanical and Aerospace Engineering Department, University of California Los Angeles, Los Angeles, California, United States of America, 3 School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America Abstract The ability to control cellular functions can bring about many developments in basic biological research and its applications. The presence of multiple signals, internal as well as externally imposed, introduces several challenges for controlling cellular functions. Additionally the lack of clear understanding of the cellular signaling network limits our ability to infer the responses to a number of signals. This work investigates the control of Kaposi’s sarcoma-associated herpesvirus reactivation upon treatment with a combination of multiple signals. We utilize mathematical model-based as well as experiment-based approaches to achieve the desired goals of maximizing virus reactivation. The results show that appropriately selected control signals can induce virus lytic gene expression about ten folds higher than a single drug; these results were validated by comparing the results of the two approaches, and experimentally using multiple assays. Additionally, we have quantitatively analyzed potential in