tailieunhanh - Báo cáo y học: " Inhibition of HIV-1 replication by small interfering RNAs directed against Glioma Pathogenesis Related Protein (GliPR) expression"

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: " Inhibition of HIV-1 replication by small interfering RNAs directed against Glioma Pathogenesis Related Protein (GliPR) expression. | Capalbo et al. Retrovirology 2010 7 26 http content 7 1 26 RETROVIROLOGY RESEARCH Open Access Inhibition of HIV-1 replication by small interfering RNAs directed against Glioma Pathogenesis Related Protein GliPR expression 1 1 2 1 1 1 Gianni Capalbo Thea Muller-Kuller Ursula Dietrich Dieter Hoelzer Oliver G Ottmann Urban J Scheuring Abstract Background Previously we showed that glioma pathogenesis related protein GliPR is induced in CEM T cells upon HIV-1 infection in vitro. To examine whether GliPR plays a role as HIV dependency factor HDF we tested the effect of GliPR suppression by siRNA on HIV-1 replication. Results Induction of GliPR expression by HIV-1 was confirmed in P4-CCR5 cells. When GliPR was suppressed by siRNA HIV-1 replication was significantly reduced as measured by HIV-1 transcript levels HIV-1 p24 protein levels and HIV-1 LTR-driven reporter gene expression suggesting that GliPR is a cellular co-factor of HIV-1. Microarray analysis of uninfected HeLa cells following knockdown of GliPR revealed among a multitude of gene expression alterations a down-regulation of syndecan-1 syndecan-2 protein kinase C alpha PRKCA the catalytic subunit b of cAMP-dependent protein kinase PRKACB nuclear receptor co-activator 3 NCOA3 and cell surface protein CD59 protectin all genes having relevance for HIV-1 pathology. Conclusions The up-regulation of GliPR by HIV-1 and the early significant inhibition of HIV-1 replication mediated by knockdown of GliPR reveal GliPR as an important HIV-1 dependency factor HDF which may be exploited for HIV-1 inhibition. Background The replication of HIV-1 depends on specific host factors 1-4 . A recent report identified 273 cellular HIV-1 dependency factors HDF that are important for HIV-1 replication 5 . Furthermore HIV-1 modifies the mRNA expression of a relatively large number of host cell genes as shown by several reports 6-10 . Differential display experiments suggested that the expression of 700 host genes .