Human SCARB2-Mediated Entry and Endocytosis of EV71

Enterovirus (EV) 71 infection is known to cause hand-foot-and-mouth disease (HFMD) and in severe cases, induces neurological disorders culminating in fatality. An outbreak of EV71 in South East Asia in 1997 affected over 120,000 people and caused neurological disorders in a few individuals. The control of EV71 infection through public health interventions remains minimal and treatments are only symptomatic. Recently, human scavenger receptor class B, member 2 (SCARB2) has been reported to be a cellular receptor of EV71. We expressed human SCARB2 gene in NIH3T3 cells (3T3-SCARB2) to study the mechanisms of EV71 entry and infection. We demonstrated that human SCARB2 serves as a cellular receptor for EV71 entry. Disruption of expression of SCARB2 using siRNAs can interfere EV71 infection and subsequent inhibit the expression of viral capsid proteins in RD and 3T3-SCARB2 but not Vero cells. SiRNAs specific to clathrin or dynamin or chemical inhibitor of clathrin-mediated endocytosis were all capable of interfering with the entry of EV71 into 3T3-SCARB2 cells. On the other hand, caveolin specific siRNA or inhibitors of caveolae-mediated endocytosis had no effect, confirming that only clathrin-mediated pathway was involved in EV71 infection. Endocytosis of EV71 was also found to be pH-dependent requiring endosomal acidification and also required intact membrane cholesterol. In summary, the mechanism of EV71 entry through SCARB2 as the receptor for attachment, and its cellular entry is through a clathrin-mediated and pH-dependent endocytic pathway. This study on the receptor and endocytic mechanisms of EV71 infection is useful for the development of effective medications and prophylactic treatment against the enterovirus

Canalicular microdomains and bile formation

This book is the proceedings of the XX International Bile Acid Meeting, Falk Symposium 165 entitled ‘Bile Acid Biology and Therapeutic Actions’, held in Amsterdam, The Netherlands, June 13--14, 2008, and dedicated to both basic and clinical aspects of bile acid research with a focus on the role of bile acids in hepatobiliary diseases. The latest findings are presented by leading scientists and clinicians in the field. Since the last International Bile Acid Meeting in Freiburg im Breisgau, Germany, in 2006, bile acid research has continued to flourish and therapeutic use of bile acids has attained a broader role. New insights have been gained into the mechanisms responsible for maintenance of bile acid homeostasis, and effects of bile acids on the cell signalling pathways have been further elucidated. Knowledge about the genetic basis of bile acid physiology has further increased. Therapy of chronic cholestatic liver diseases with ursodeoxycholic acid and new aspects of its chemopreventive properties continue to stimulate basic and clinical research and contribute to the understanding of underlying modes of action and to optimized treatment schedules