PubMed:35216446 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/35216446","sourcedb":"PubMed","sourceid":"35216446","source_url":"https://www.ncbi.nlm.nih.gov/pubmed/35216446","text":"Engineered Zinc Finger Protein Targeting 2LTR Inhibits HIV Integration in Hematopoietic Stem and Progenitor Cell-Derived Macrophages: In Vitro Study.\nHuman hematopoietic stem/progenitor cell (HSPC)-based gene therapy is a promising direction for curing HIV-1-infected individuals. The zinc finger protein (2LTRZFP) designed to target the 2-LTR-circle junction of HIV-1 cDNA was previously reported as an intracellular antiviral molecular scaffold that prevents HIV integration. Here, we elucidate the efficacy and safety of using 2LTRZFP in human CD34+ HSPCs. We transduced 2LTRZFP which has the mCherry tag (2LTRZFPmCherry) into human CD34+ HSPCs using a lentiviral vector. The 2LTRZFPmCherry-transduced HSPCs were subsequently differentiated into macrophages. The expression levels of pro-apoptotic proteins of the 2LTRZFPmCherry-transduced HSPCs showed no significant difference from those of the non-transduced control. Furthermore, the 2LTRZFPmCherry-transduced HSPCs were successfully differentiated into mature macrophages, which had normal phagocytic function. The cytokine secretion assay demonstrated that 2LTRZFPmCherry-transduced CD34+ derived macrophages promoted the polarization towards classically activated (M1) subtypes. More importantly, the 2LTRZFPmCherry transduced cells significantly exhibited resistance to HIV-1 integration in vitro. Our findings demonstrate that the 2LTRZFPmCherry-transduced macrophages were found to be functionally and phenotypically normal, with no adverse effects of the anti-HIV-1 scaffold. Our data suggest that the anti-HIV-1 integrase scaffold is a promising antiviral molecule that could be applied to human CD34+ HSPC-based gene therapy for AIDS patients.","tracks":[{"project":"Test-merged","denotations":[{"id":"1075","span":{"begin":11,"end":30},"obj":"Gene"},{"id":"1076","span":{"begin":41,"end":45},"obj":"Gene"},{"id":"1077","span":{"begin":55,"end":58},"obj":"Species"},{"id":"1078","span":{"begin":285,"end":304},"obj":"Gene"},{"id":"1079","span":{"begin":547,"end":551},"obj":"Gene"},{"id":"1080","span":{"begin":636,"end":640},"obj":"Gene"},{"id":"1081","span":{"begin":1142,"end":1146},"obj":"Gene"},{"id":"1082","span":{"begin":1661,"end":1665},"obj":"Gene"},{"id":"1083","span":{"begin":461,"end":464},"obj":"Species"},{"id":"1084","span":{"begin":530,"end":537},"obj":"Chemical"},{"id":"1085","span":{"begin":150,"end":155},"obj":"Species"},{"id":"1086","span":{"begin":363,"end":368},"obj":"Species"},{"id":"1087","span":{"begin":1655,"end":1660},"obj":"Species"},{"id":"1088","span":{"begin":1571,"end":1576},"obj":"Species"},{"id":"1089","span":{"begin":1331,"end":1336},"obj":"Species"},{"id":"1090","span":{"begin":630,"end":635},"obj":"Species"},{"id":"1091","span":{"begin":1524,"end":1529},"obj":"Species"},{"id":"1092","span":{"begin":541,"end":546},"obj":"Species"},{"id":"1093","span":{"begin":253,"end":267},"obj":"Disease"},{"id":"1094","span":{"begin":1695,"end":1699},"obj":"Disease"},{"id":"1095","span":{"begin":1700,"end":1708},"obj":"Species"}],"attributes":[{"id":"A1077","pred":"resolved_to","subj":"1077","obj":"11676"},{"id":"A1079","pred":"resolved_to","subj":"1079","obj":"947"},{"id":"A1080","pred":"resolved_to","subj":"1080","obj":"947"},{"id":"A1081","pred":"resolved_to","subj":"1081","obj":"947"},{"id":"A1082","pred":"resolved_to","subj":"1082","obj":"947"},{"id":"A1083","pred":"resolved_to","subj":"1083","obj":"11676"},{"id":"A1084","pred":"resolved_to","subj":"1084","obj":"-"},{"id":"A1085","pred":"resolved_to","subj":"1085","obj":"9606"},{"id":"A1086","pred":"resolved_to","subj":"1086","obj":"11676"},{"id":"A1087","pred":"resolved_to","subj":"1087","obj":"9606"},{"id":"A1088","pred":"resolved_to","subj":"1088","obj":"11676"},{"id":"A1089","pred":"resolved_to","subj":"1089","obj":"11676"},{"id":"A1090","pred":"resolved_to","subj":"1090","obj":"9606"},{"id":"A1091","pred":"resolved_to","subj":"1091","obj":"11676"},{"id":"A1092","pred":"resolved_to","subj":"1092","obj":"9606"},{"id":"A1093","pred":"resolved_to","subj":"1093","obj":"MESH:D015490"},{"id":"A1094","pred":"resolved_to","subj":"1094","obj":"MESH:D000163"},{"id":"A1095","pred":"resolved_to","subj":"1095","obj":"9606"},{"subj":"1075","pred":"source","obj":"Test-merged"},{"subj":"1076","pred":"source","obj":"Test-merged"},{"subj":"1077","pred":"source","obj":"Test-merged"},{"subj":"1078","pred":"source","obj":"Test-merged"},{"subj":"1079","pred":"source","obj":"Test-merged"},{"subj":"1080","pred":"source","obj":"Test-merged"},{"subj":"1081","pred":"source","obj":"Test-merged"},{"subj":"1082","pred":"source","obj":"Test-merged"},{"subj":"1083","pred":"source","obj":"Test-merged"},{"subj":"1084","pred":"source","obj":"Test-merged"},{"subj":"1085","pred":"source","obj":"Test-merged"},{"subj":"1086","pred":"source","obj":"Test-merged"},{"subj":"1087","pred":"source","obj":"Test-merged"},{"subj":"1088","pred":"source","obj":"Test-merged"},{"subj":"1089","pred":"source","obj":"Test-merged"},{"subj":"1090","pred":"source","obj":"Test-merged"},{"subj":"1091","pred":"source","obj":"Test-merged"},{"subj":"1092","pred":"source","obj":"Test-merged"},{"subj":"1093","pred":"source","obj":"Test-merged"},{"subj":"1094","pred":"source","obj":"Test-merged"},{"subj":"1095","pred":"source","obj":"Test-merged"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"Test-merged","color":"#ec93ab","default":true}]}]}}