the host cell sulfonation pathway contributes to retroviral infection at a step coincident with provirus establishment逆转录病毒感染宿主细胞磺化途径贡献在与原病毒的步骤一致.pdf

The Host Cell Sulfonation Pathway Contributes to Retroviral Infection at a Step Coincident with Provirus Establishment 1 1,2 3 James W. Bruce , Paul Ahlquist *, John A. T. Young * 1 Institute for Molecular Virology, University of Wisconsin, Madison, Wisconsin, United States of America, 2 Howard Hughes Medical Institute University of Wisconsin, Madison, Wisconsin, United States of America, 3 Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, California, United States of America Abstract The early steps of retrovirus replication leading up to provirus establishment are highly dependent on cellular processes and represent a time when the virus is particularly vulnerable to antivirals and host defense mechanisms. However, the roles played by cellular factors are only partially understood. To identify cellular processes that participate in these critical steps, we employed a high volume screening of insertionally mutagenized somatic cells using a murine leukemia virus (MLV) vector. This approach identified a role for 3 9-phosphoadenosine 59-phosphosulfate synthase 1 (PAPSS1), one of two enzymes that synthesize PAPS, the high energy sulfate donor used in all sulfonation reactions catalyzed by cellular sulfotransferases. The role of the cellular sulfonation pathway was confirmed using chemical inhibitors of PAPS synthases and cellular sulfotransferases. The requirement for sulfonation was mapped to a stage during or shortly after MLV provirus establishment and influenced subsequent gene expression from the viral long terminal repeat (LTR) promoter. Infection of cells by an HIV vector was also shown to be highly dependent on the cellular sulfonation pathway. T