?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%2F32360%2F&rft.title=Siglec-10%2C+CD1B%2C+and+Palladin+are+differentially+expressed+between+Human+Immunodeficiency+Virus%2B+(HIV)+progressors+and+nonprogressors&rft.creator=Clunk%2C+Marilee&rft.description=HIV+plasma+viremia+and+CD4%2B+lymphocyte+counts+dictate+the+classification+of+HIV%2B+disease+progression+to+Acquired+Immunodeficiency+Syndrome+(AIDS)%2C+i.e.+progressor+(PR)+vs.+non-progressor+(NP).+In+the+absence+of+antiretroviral+therapy%2C+NP+CD4%2B+counts+remain+stable+and+plasma+viremia+is+substantially+reduced.+Recent+data+affirms+that+NPs+exhibit+decreased+trans-infection+efficiency+due+to+reduced+cellular+cholesterol+levels+in+antigen+presenting+cells+(APCs)+through+cholesterol+efflux+protein%2C+ABCA-1.+Because+defective+trans+infection+in+NPs+was+also+observed+prior+to+seroconversion%2C+it+is+believed+that+nonprogression+is+influenced+by+a+genetic+trait.+Further+transcriptome+analysis+of+Multicenter+AIDS+Cohort+Study+(MACS)+immature+dendritic+cells+(iDCs)+reveals+elevated+expression+profiles+for+Siglec-10%2C+CD1B%2C+and+Palladin+(PALLD)+in+NPs+compared+to+PRs.+While+the+explicit+mechanism+remains+elusive%2C+our+aim+is+to+elucidate+the+genetic+origin+of+NP+viremic+control.+I+have+hypothesized+that+upregulated+expression+of+Siglec-10%2C+CD1b%2C+and+Palladin+in+HIV%2B+MACS+NPs+is+responsible+for+control+of+HIV+progression+by+attenuating+trans+infection+between+iDCs+and+CD4+lymphocytes+through+unrelated+molecular+and+immunological+mechanisms.%0D%0AMACS+CD14%2B+monocytes+were+cultured+with+IL-4+and+GM-CSF+to+yield+iDCs.+Protein+expression+of+Siglec-10%2C+CD1B%2C+and+PALLD+in+seronegative+(SN)%2C+PR%2C+and+NP+iDCs+has+been+assessed+using+flow+cytometry.+Quantitative+PCR+(qPCR)+analysis+of+MACS+iDCs+RNA+is+used+for+corroboration+of+gene+expression+data+from+the+transcriptome+findings.+TaqMan%C2%AE+SNP+genotyping+assays+examined+if+there+is+a+link+between+NP+disease+state+and+single+base-pair+variations+within+DNA.%0D%0AFlow+cytometry+shows+no+significant+difference+in+Siglec-10%2C+CD1b%2C+or+PALLD+protein+expression+levels+between+PR+and+NP+donors.+SyBr+green+qPCR+primers+for+resulted+in+artefactual+amplicons+for+control+and+experimental+melt+curves.+IDT+Taq-Man%C2%AE+primers+were+subsequently+designed.+Analysis+of+qPCR+data+shows+significant+differences+in+CD1b+and+PALLD+expression+levels+between+NPs+and+PRs+(p+%3C+0.05).+Haplotype+analysis+of+CD1b+SNPs+between+NP%2C+PR%2C+and+SN+individuals+via+TaqMan+Genotyping+was+not+statistically+significant.%0D%0APublic+Health+Significance%3A+Identifying+the+underlying+genetic+factors+that+drive+HIV-1+disease+progression+could+reveal+potential+therapeutic+targets+with+the+long+term+aims+of+improving+HIV+health+outcomes.&rft.date=2017-09-25&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%2F32360%2F1%2Fclunkmj_etd_gsphAug2017_Final.pdf&rft.identifier=++Clunk%2C+Marilee++(2017)+Siglec-10%2C+CD1B%2C+and+Palladin+are+differentially+expressed+between+Human+Immunodeficiency+Virus%2B+(HIV)+progressors+and+nonprogressors.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++