Báo cáo y học: "Vpx rescues HIV-1 transduction of dendritic cells from the antiviral state established by type 1 interferon"

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: Vpx rescues HIV-1 transduction of dendritic cells from the antiviral state established by type 1 interferon. | Pertel et al. Retrovirology 2011 8 49 http content 8 1 49 RETR0VIR0L0GY RESEARCH Open Access Vpx rescues HIV-1 transduction of dendritic cells from the antiviral state established by type 1 interferon Thomas Pertel Christian Reinhard and Jeremy Luban Abstract Background Vpx is a virion-associated protein encoded by SIVSM a lentivirus endemic to the West African sooty mangabey Cercocebus atys . HIV-2 and SIVMAC zoonoses resulting from SIVSM transmission to humans or Asian rhesus macaques Macaca mulatta also encode Vpx. In myeloid cells Vpx promotes reverse transcription and transduction by these viruses. This activity correlates with Vpx binding to DCAF1 VPRBP and association with the DDB1 RBX1 CUL4A E3 ubiquitin ligase complex. When delivered experimentally to myeloid cells using VSV G-pseudotyped virus-like particles VLPs Vpx promotes reverse transcription of retroviruses that do not normally encode Vpx. Results Here we show that Vpx has the extraordinary ability to completely rescue HIV-1 transduction of human monocyte-derived dendritic cells MDDCs from the potent antiviral state established by prior treatment with exogenous type 1 interferon IFN . The magnitude of rescue was up to 1 000-fold depending on the blood donor and was also observed after induction of endogenous IFN and IFN-stimulated genes ISGs by LPS poly I C or poly dA dT . The effect was relatively specific in that Vpx-associated suppression of soluble IFN P production of mRNA levels for ISGs or of cell surface markers for MDDC differentiation was not detected. Vpx did not rescue HIV-2 or SIVMAC transduction from the antiviral state even in the presence of SIVMAC or HIV-2 VLPs bearing additional Vpx or in the presence of HIV-1 VLPs bearing all accessory genes. In contrast to the effect of Vpx on transduction of untreated MDDCs HIV-1 rescue from the antiviral state was not dependent upon Vpx interaction with DCAF1 or on the presence of DCAF1 within the MDDC target cells. .

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