?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F16998%2F&rft.title=The+Effect+of+Epstein-Barr+Virus+Latent+Membrane+Protein+2+Expression+on+the+Kinetics+of+Early+B+Cell+Infection+and+Immortalization&rft.creator=Wasil%2C+Laura+R.&rft.description=Epstein-Barr+virus+(EBV)+has+been+associated+with+the+development+of+several+human+malignancies.+Infection+of+B+cells+with+wild-type+EBV+in+vitro+leads+to+activation+and+proliferation+that+result+in+efficient+production+of+lymphoblastoid+cell+lines+(LCLs).+The+majority+of+latent+genes+are+expressed+during+early+infection%2C+including+latent+membrane+protein+2+(LMP2).+Currently%2C+the+role+of+LMP2+in+B+cell+proliferation+is+controversial%3B+some+studies+have+shown+that+LMP2+is+dispensable%2C+while+others+report+it+is+important+role+for+this+process.+However%2C+each+of+these+experimental+systems+were+limited+by+either+wild-type+virus+contamination+or+use+of+incomplete+viral+genomes+(mini-EBV)%2C+which+precluded+clear+assessments+of+the+effects+of+LMP2+during+early+infection.+%0D%0AIn+this+study+I+investigated+the+effect+of+LMP2+on+early+B+cell+infection+and+subsequent+immortalization+via+complete+recombinant+EBV+with+knockouts+of+either+or+both+isoforms+of+the+LMP2+gene%2C+LMP2A+and+LMP2B+(%CE%942A%2C+%CE%942B+and+%CE%942A%2F%CE%942B).+Infection+of+B+cells+with+LMP2A+knockout+viruses+resulted+in+marked+decreases+in+activation+and+proliferation+relative+to+wild-type%2C+and+higher+percentages+of+apoptotic+B+cells.+%CE%942B+virus+infection+exhibited+activation+levels+comparable+to+wild-type%2C+but+with+fewer+numbers+of+proliferating+B+cells.+The+stability+of+viral+latency+was+determined+for+early+B+cell+infection+by+evaluating+latent+and+lytic+gene+expression+with+or+without+lytic+stimulation+via+the+B+cell+receptor+(BCR).+Infection+with+wild-type%2C+%CE%942A+and+%CE%942B+viruses+with+or+without+BCR+stimulation+did+not+result+in+changes+in+viral+latency%2C+whereas+stimulation+of+BCR+signaling+in+%CE%942A%2F%CE%942B-infected+cells+resulted+in+decreased+LMP1+expression%2C+suggesting+loss+of+stability+in+viral+latency.+The+long-term+effects+of+LMP2+deletion+on+B+cell+outgrowth+were+investigated+using+LCL+establishment+assays%2C+which+revealed+that+LMP2A%2C+but+not+LMP2B%2C+is+critical+for+efficient+immortalization+of+B+cells+in+vitro.+Loss+of+both+isoforms+promoted+the+least+activation%2C+proliferation+and+LCL+formation.+This+study+enhances+our+knowledge+of+events+required+for+B+cell+transformation+by+EBV%2C+and+clearly+shows+the+public+health+relevance+of+understanding+genes+involved+in+tumorigenesis+for+the+future+pursuit+of+more+effective+treatments+for+EBV-associated+malignancies.&rft.date=2013-01-29&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F16998%2F1%2FETD_Laura_Rose_Wasil_December_2012_v.4.pdf&rft.identifier=++Wasil%2C+Laura+R.++(2013)+The+Effect+of+Epstein-Barr+Virus+Latent+Membrane+Protein+2+Expression+on+the+Kinetics+of+Early+B+Cell+Infection+and+Immortalization.++Doctoral+Dissertation%2C+University+of+Pittsburgh.++++(Unpublished)++