TAILIEUCHUNG - Báo cáo sinh học: "Altering a-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism"

Tuyển tập các báo cáo nghiên cứu về sinh học được đăng trên tạp chí sinh học Journal of Biology đề tài: Altering a-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism | Dylla et al. Genetic Vaccines and Therapy 2011 9 8 http content 9 1 8 GENETIC VACCINES AND THERAPY RESEARCH Open Access Altering a-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism l ipii Idlpc p mvlIp1 2 I itpi ip2 npipip p i lirhp p4 tp pp 10 in 75 PnH Ppi li R i lc _cv lr1 2 3 Douglds E Dylld Litdo Ale Ddniei E IVlidlele Sleldll Kunz dl Id Pdul B IVicCrdy JI Abstract Background The envelope glycoprolein of lymphocytic choriomeningitis virus LCMV cdn efficiently pseudotype lentivirdl vectors. Some slrdins of LCMV exploit high dffinity interactions with a-dyslroglycdn a-DG lo bind lo cell surfdces dnd subsequently fuse in low pH endosomes. LCMV strains with low a-DG dffinity utilize dn unknown receptor dnd displdy unique tissue tropisms. We pseudotyped non-primdte feline immunodeficiency virus FIV vectors using LCMV derived glycoproteins with high or low dffinity to a-DG dnd evdludted their properties in vitro dnd in vivo. Methods We pseudotyped FIV with the LCMV WE54 strain envelope glycoprotein dnd dlso engineered d point mutdtion in the WE54 envelope glycoprotein L260F to diminish a-DG dffinity dnd direct binding to dlterndte receptors. We hypothesized thdt this chdnge would dlter in vivo tissue tropism dnd enhdnce gene transfer to neondtdl dnimdls. Results In mice hepdtic a- dnd p-DG expression wds gredtest dt the ldte gestdtiondl dnd neondtdl time points. When displdyed on the surfdce of the FIV lentivirus the WE54 L260F mutdnt glycoprotein bound wedkly to immobilized a-DG. Additiondlly LCMV WE54 pseudotyped FIV vector transduction wds neutralized by pre-incubdtion with soluble a-DG while the mutdnt glycoprotein pseudotyped vector wds not. In vivo gene transfer in ddult mice with either envelope yielded low transduction efficiencies in hepdtocytes following intravenous delivery. In mdrked contrast neondtdl gene transfer with the LCMV envelopes dnd notdbly with the FIV-L260F vector conferred

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