hcv causes chronic endoplasmic reticulum stress leading to adaptation and interference with the unfolded protein response丙肝病毒引起慢性内质网应激导致适应和干扰展开的蛋白质反应.pdfVIP

HCV Causes Chronic Endoplasmic Reticulum Stress Leading to Adaptation and Interference with the Unfolded Protein Response 1 1 3 4 5 Emmanuelle Merquiol , Dotan Uzi , Tobias Mueller , Daniel Goldenberg , Yaakov Nahmias , Ramnik J. 6 2. 7 . Xavier , Boaz Tirosh , Oren Shibolet * 1 Liver Unit, Division of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel, 2 Institute for Drug Research, School of Pharmacology, Faculty of ´ ¨ Medicine, Jerusalem, Israel, 3 Medizinische Klinik M. S. Hepatologie und Gastroenterologie, Charite -Universitatsmedizin Berlin, CVK, Berlin, Germany, 4 Goldyne Savad Institute of Gene Therapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel, 5 Center for Bioengineering, Rachel and Selim Benin School of Computer Science and Engineering, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel, 6 Gastroenterology Unit, Center for the Study of Inflammatory Bowel Disease, and Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, United States of America, 7 Liver Unit, Department of Gastroenterology and Liver Disease, Tel-Aviv Sourasky Medical-Center, Tel-Aviv, Israel Abstract Background: The endoplasmic reticulum (ER) is the cellular site for protein folding. ER stress occurs when protein folding capacity is exceeded. This stress induces a cyto-protective signaling cascades termed the unfolded protein response (UPR) aimed at restoring homeostasis. While acute ER stress is lethal, chronic sub-lethal ER stress causes cells