?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%2F6861%2F&rft.title=EFFECT+OF+HIV-1+VIRAL+PROTEIN+R+(VPR)+ON+T+CELL+TARGETS%3A+CONSEQUENCES+IN+IMMUNOSUPPRESSION+AND+VIRAL+DISSEMINATION&rft.creator=Venkatachari%2C+Narasimhan+Jayanth&rft.description=CD4%2BT-cells+have+a+central+role+in+induction+and+homeostasis+of+the+immune+response%2C+and+are+also+the+major+target+cells+for+HIV.+HIV+has+devised+mechanisms+to+subvert+the+immune+system+and+further+its+cause+of+survival+and+dissemination.+vpr+is+one+of+the+accessory+genes%2C+which+is+essential+for+the+virus+survival+in+vivo.+Being+a+soluble+protein+with+an+ability+to+transduce+across+cell+membranes%2C+Vpr+can+potentially+affect+bystander+cells.+We+hypothesize+that+HIV-1+Vpr+alters+the+functions+of+both+infected+and+bystander+T+lymphocytes%2C+utilizing+direct+and+indirect+mechanisms%2C+and+these+Vpr-mediated+effects+contribute+in+part+to+the+immune+dysregulation%2C+and+aid+in+viral+dissemination.+The+Specific+Aims+of+this+proposal+are+to%3A+(1)+Assess+the+immune+modulatory+effects+of+Vpr+in+infected+and+bystander+T-lymphocytes%3B+(2)+Understand+the+role+of+Vpr+in+T+lymphocytes%2C+natural+killer+(NK)+cells+and+dendritic+cells+(DC)+interactions%3B+and+(3)+Analyze+the+structure-function+role+of+Vpr+in+immunopathogenesis.+We+utilized+HIV-1wt+and+HIV-1%CE%94Vpr+viruses+and+compared+the+difference+in+the+effects+of+these+viruses+under+controlled+simulated+invitro+conditions.+The+differences+observed+in+the+effect+of+these+two+viruses+can+be+attributed+to+Vpr+provided+that+the+infections+in+both+the+experimental+sets+are+similar.+In+some+studies%2C+to+clearly+identify+infected+cells%2C+we+employed+EGFP+reporter+viruses.+The+effects+in+infected+cells+and+bystander+cells+were+evaluated.+Results+indicate+that+HIV-1+Vpr+has+a+role+in+dysregulation+of+immune+cells+during+HIV+infection.+Vpr+differentially+regulates+the+surface+expression+of+T+cell+costimulatory+molecules%2C+CD28+and+CTLA-4%2C+and+inhibits+IFN-%CE%B3+production+in+infected+T+cells.+Vpr+also+inhibits+NK+cell+function+by+augmenting+TGF-%CE%B2+production+and+inducing+altered+expression+of+NK+receptor+ligands.+Further%2C+oligomerization+of+Vpr+has+a+role+in+gag+incorporation+of+Vpr+and+in+viral+pathogenesis.+The+findings+presented+in+this+study+are+significant+for+public+health+because+mechanistic+understanding+of+the+pathogenesis+will+aid+in+development+of+novel+anti-viral+therapeutics.&rft.date=2009-06-29&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%2F6861%2F1%2FJay_ETD.pdf&rft.identifier=++Venkatachari%2C+Narasimhan+Jayanth++(2009)+EFFECT+OF+HIV-1+VIRAL+PROTEIN+R+(VPR)+ON+T+CELL+TARGETS%3A+CONSEQUENCES+IN+IMMUNOSUPPRESSION+AND+VIRAL+DISSEMINATION.++Doctoral+Dissertation%2C+University+of+Pittsburgh.++++(Unpublished)++