a major determinant of cyclophilin dependence and cyclosporine susceptibility of hepatitis c virus identified by a genetic approach还有依赖的主要决定因素和环孢霉素c型肝炎病毒的易感性基因的方法.pdfVIP

A Major Determinant of Cyclophilin Dependence and Cyclosporine Susceptibility of Hepatitis C Virus Identified by a Genetic Approach 1 1 1 1 2 2 Feng Yang , Jason M. Robotham , Henry Grise , Stephen Frausto , Vanesa Madan , Margarita Zayas , 2 3 3 1 4 Ralf Bartenschlager , Margaret Robinson , Andrew E. Greenstein , Anita Nag , Timothy M. Logan , Ewa 5 1 Bienkiewicz , Hengli Tang * 1 Department of Biological Science, Florida State University, Tallahassee, Florida, United States of America, 2 Department of Infectious Diseases, Molecular Virology, University of Heidelberg, Heidelberg, Germany, 3 Gilead Sciences, Foster City, California, United States of America, 4 Department of Chemistry, Florida State University, Tallahassee, Florida, United States of America, 5 Department of Biomedical Sciences, Florida State University, Tallahassee, Florida, United States of America Abstract Since the advent of genome-wide small interfering RNA screening, large numbers of cellular cofactors important for viral infection have been discovered at a rapid pace, but the viral targets and the mechanism of action for many of these cofactors remain undefined. One such cofactor is cyclophilin A (CyPA), upon which hepatitis C virus (HCV) replication critically depends. Here we report a new genetic selection scheme that identified a major viral determinant of HCV’s dependence on CyPA and susceptibility to cyclosporine A. We selected mutant viruses that were able to infect CyPA- knockdown cells which were refracto