Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: b-TrCP is dispensable for Vpu’s ability to overcome the CD317/Tetherin-imposed restriction to HIV-1 release. | Tervo et al. Retrovirology 2011 8 9 http content 8 1 9 RETROVIROLOGY RESEARCH Open Access P-TrCP is dispensable for Vpu s ability to overcome the CD317 Tetherin-imposed restriction to HIV-1 release 1 1 1 1 1 Hanna-Mari Tervo Stefanie Homann Ina Ambiel Joelle V Fritz Oliver T Fackler Oliver T Keppler Abstract Background The cellular transmembrane protein CD317 BST-2 Tetherin restricts HIV-1 infection by physically tethering mature virions to the surface of infected cells. HIV-1 counteracts this restriction by expressing the accessory protein Vpu yet the mechanism of this antagonism is incompletely understood. p-TrCP is the substrate recognition domain of an E3 ubiquitin ligase complex that interacts with the di-serine motif S52 S56 in the cytoplasmic tail of Vpu to target the CD4 receptor for proteasomal degradation. Recently it has been suggested that p-TrCP is also critically involved in Vpu s ability to overcome the CD317-mediated virion release block. Results To test this model we analyzed the consequences of several experimental strategies to interfere with the Vpu-p-TrCP protein-protein interaction. Under these conditions we studied effects of Vpu on expression and localization of CD317 and CD4 as well as on its ability to promote HIV-1 release. Our results demonstrate a strict requirement for Vpu s di-serine motif for degradation of CD4 and also CD317 reduction of cell surface exposure of CD317 and HIV-1 release enhancement. We further show a critical role of p-TrCP2 but not of the structurally related P-TrCP1 isoform for Vpu-mediated degradation of both receptors. Most importantly Vpu remained active in downregulating CD317 from the cell surface and in overcoming the HIV-1 release restriction in p-TrCP-depleted cells. Conclusions These results demonstrate that p-TrCP is not strictly required for Vpu s ability to counteract the CD317-imposed virion release block and support the relevance of cell surface down-modulation of the
