Is was performed by Student's t test, and differences wereIs was performed by Student's t

Is was performed by Student’s t test, and differences were
Is was performed by Student’s t test, and differences were considered significant at a value of p < 0.05.Discussion HPBP is a member of the DING protein family identified in eukaryotes for their implication in diverse biological processes [28,37]. Here, we show that the human phosphate binding protein has PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28827318 a potent anti HIV-1 activity. Previous observations suggested that p27 SJ , another member of the DING protein family isolated from the plant Hypericum perforatum, represses HIV-1 replication and transcription [25,45,46]. However, it is noteworthy to precise that this inhibitor effect is dose dependent. Indeed it was shown by the same group thatCherrier et al. Virology Journal 2011, 8:352 http://www.virologyj.com/content/8/1/Page 4 ofFigure 1 HPBP represses HIV-1 gene transcription and replication. 1G5 cells were transfected with the pNL4.3 provirus. (1) Mock, (2) HPBP/ HPNO1 (50 nM), (3) HPBP (50 nM), (4) HPON1 (50 nM), and (5) AZT (10 M) was added 24 h post transfection. Luciferase activity (A) and HIV-1 replication (B) were monitored 48 h post transfection. Values correspond to an average of at least three independent experiments carried out in duplicate. The purity and the size of purified-HPBP were controlled by SDS-PAGE and coomassie blue staining (C).p27SJ has a dual role on MCP1(monocyte chemoattractant protein 1) gene transcription being an activator at low 4F-Benzoyl-TN14003 solubility concentration and an inhibitor at high concentration [47]. This lead us to hypothesize that HPBP might also have antiviral activities. Since CD4+ T lymphocytes PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27741243 and cells from monocyte-macrophage lineages are major targets for HIV-1, we assessed the in vitro antiviral activity of HPBP in lymphoblastoid cell lines (Jurkat), primary monocyte/macrophage cells and peripheral blood lymphocytes presenting laboratory and clinicalisolates of HIV-1. The inhibitory effect of HPBP on HIV-1 replication is very strong, the IC50 value being in the range of 5 nM to 10 nM, and also compared to other canonical drugs currently used in HAART (15 nM to 6.7 M for AZT and 40 nM to 8.5 M for tenofivir) [48]. At this concentration HPBP is also a potent anti HIV-1 drug in PBL and in primary macrophages, which is not true for several other anti HIV-1 drugs. For example, 3 RT inhibitors, i.e. Lamivudine, entricitabine and AZT have different IC50 values when assessed for their antiviral activity in PBL and macrophages [49]. Furthermore, the CC50 values for HPBP were in the range of 140 nM to 200 nM and the selectivity index CC50/IC50 (ratio between the toxic dose and the inhibitory dose) of HPBP was in the range of 28 to 40. This high ratio indicates that the therapeutical index should therefore be high enough for use in in vivo studies. HPBP also emerged as a promising candidate for drug development as it targets HIV-1 transcription, a phase of the HIV-1 cycle not yet targeted by other drugs. In productive cells, the transcription of the provirus DNA is regulated by the interplay of a combination of viral and cellular transcription factors [50-53]. Darbinian and coll. have identified the protein P27SJ, which belongs to the DING protein family and inhibits the activity of theFigure 2 Dose response and cytotoxicity test. 1G5 cells were infected with NL4-3 and treated with increasing amount of HPBP 24 h post transfection. Luciferase activity was assessed 48 h post transfection. MTT test were performed in the same conditions than the dose response experiment. HIV-1 inhibition (grey columns) and percentage.