?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%2F19575%2F&rft.title=Role+of+HIV-1+Vpr+on+Host-Cellular+Functions%3A+Cell-Specific+Analysis+in+Productively-Infected+Macrophages&rft.creator=Sparks%2C+Jessica&rft.description=Progression+of+human+immunodeficiency+virus+type+1+(HIV-1)+pathogenesis+impedes+on+the+patient%E2%80%99s+ability+to+combat+foreign+pathogens+by+infecting+immune+cells%2C+a+disease+commonly+referred+to+as+acquired+immunodeficiency+syndrome+(AIDS).++In+addition+to+the+onset+of+AIDS%2C+HIV-1+is+known+to+cause+other+health+issues+over+time%2C+including+cardiovascular+disease%2C+premature+aging%2C+neurocognitive+impairment%2C+and+dementia.++The+quality+of+life+for+HIV-1-positive+patients+has+drastically+increased+with+the+introduction+of+highly+active+anti-retroviral+therapies+(HAART).++Though+the+use+of+HAART+treatments+lower+the+incidence+of+HIV-1-associated+comorbidities%2C+including+dementia%2C+more+understanding+on+HIV-1-associated+comorbidities+is+necessary+to+help+further+improve+the+quality+of+life+for+HIV-1-positive+patients%2C+which+is+of+considerable+public+health+significance.+%0D%0AThis+study+focuses+on+the+role+of+the+HIV-1+accessory+protein+viral+protein+R+(Vpr)+in+HIV-1+pathogenesis.++Previous+studies+in+our+laboratory+have+established+a+role+for+Vpr+in+HIV-1+immunopathogenesis+and+neuropathogenesis%2C+particularly+in+the+modulation+of+cytokines+and+chemokines%2C+including+IL-8+and+IL-1%CE%B2%2C+in+monocyte-derived+macrophages+and+dendritic+cells.++These+proinflammatory+cytokines+were+additionally+found+to+cause+immune+dysregulation+and+neuronal+injury.++As+a+result%2C+this+study+focuses+on+understanding+the+origin+of+these+cytokines+within+subpopulations+of+monocyte-derived+macrophages%3A+productively-infected+macrophages+that+are+actively+producing+virions+and+non-productively-infected+macrophages%2C+which+include+latently-infected+macrophages%2C+uninfected+macrophages%2C+and+macrophages+exposed+to+virus+particles+and+viral+proteins.++In+order+to+distinguish+between+the+two+groups%2C+reporter+viruses+were+created+that+are+capable+of+infecting+macrophages+and+expressing+the+enhanced+green+fluorescence+protein+(EGFP)+upon+replication.++Productively-infected+macrophages+were+successfully+identified+from+non-productively-infected+macrophages+by+utilizing+EGFP+expression%2C+which+allowed+for+cell-specific+analysis+of+cytokine+expression+within+the+macrophage+subpopulations.++Productively-infected+macrophages+yielded+a+decrease+in+IL-8+and+IL-1%CE%B2+when+infected+with+Vpr-deficient+(%E2%88%86Vpr)+reporter+viruses%2C+while+non-productively-infected+and+exposed+macrophages+showed+no+noticeable+difference.++Similarly%2C+a+virion+association+defective+mutant+of+Vpr+(Vpr-A30L)+resulted+in+lower+amounts+of+IL-8+expression.++These+results+elucidate+the+distinct+role+of+Vpr+in+IL-1%CE%B2+and+IL-8+expression+in+the+virion-associated+forms+and+during+de+novo+synthesis+in+productively-infected+macrophages.&rft.date=2013-09-27&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%2F19575%2F1%2FJessica_Sparks_MS_2013_ETD.pdf&rft.identifier=++Sparks%2C+Jessica++(2013)+Role+of+HIV-1+Vpr+on+Host-Cellular+Functions%3A+Cell-Specific+Analysis+in+Productively-Infected+Macrophages.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++