Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Retrovirology cung cấp cho các bạn kiến thức về ngành y đề tài: "Vpu-dependent block to incorporation of GaLV Env into lentiviral vectors. | Christodoulopoulos et al. Retrovirology 2010 7 4 http content 7 1 4 RETROVIROLOGY RESEARCH Open Access Vpu-dependent block to incorporation of GaLV Env into lentiviral vectors Ilias Christodoulopoulos Magali E Droniou-Bonzom Jill E Oldenburg Paula M Cannon Abstract Background The gibbon ape leukemia virus GaLV Env protein mediates entry into a wide range of human cells and is frequently used to pseudotype retroviral vectors. However an incompatibility exists between GaLV Env and lentiviral vectors that results in decreased steady-state levels of the mature GaLV Env in cells and prevents its incorporation into lentiviral vector particles. Results We identified the HIV-1 Vpu protein as the major cause of the depletion in GaLV Env levels that occurs when lentiviral vector components are present. This activity of Vpu targeted the mature cleaved form of the GaLV Env that exists within or beyond the trans-Golgi. The activity required two conserved phospho-serines in the cytoplasmic tail of Vpu that are known to recruit b TrCP a substrate adaptor for an SCF E3 ubiquitin ligase complex and could be blocked by mutation of lysine 618 in the GaLV Env tail. Moreover the Vpu-mediated decrease of GaLV Env levels was inhibited by the lysosomal inhibitor bafilomycin A1. Interestingly this activity of Vpu was only observed in the presence of other lentiviral vector components. Conclusions Similar to the mechanism whereby Vpu targets BST-2 tetherin for degradation these findings implicate b-TrCP-mediated ubiquitination and the endo-lysosomal pathway in the degradation of the GaLV Env by lentiviral vector components. Possibly the cytoplasmic tail of the GaLV Env contains features that mimic bona fide targets of Vpu important to HIV-1 replication. Furthermore the lack of effect of Vpu on GaLV Env in the absence of other HIV-1 proteins suggests that a more complex interaction may exist between Vpu and its target proteins with the additional involvement of one or .
