?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%2F8272%2F&rft.title=Lymphatic+Endothelial+Cells+Express+Viral+Entry+Receptors+and+Restriction+Factors&rft.creator=Bowen%2C+Christopher+David&rft.description=Lymphatic+endothelial+cells+(LECs)+line+lymphatic+vessels+and+are+present+at+mucosal+portals+of+entry+for+many+pathogens%2C+including+simian+immunodeficiency+virus+(SIV)+and+human+immunodeficiency+virus+type-1+(HIV-1).+Recent+studies+have+shown+that+LECs+express+pattern+recognition+receptors+(PRRs)%2C+such+as+Toll-like+receptors+(TLRs)%2C+capable+of+recognizing+pathogen-associated+molecular+patterns+(PAMPs).+PAMPs+are+structurally+similar+molecules+expressed+by+groups+of+pathogens.+LECs+have+also+been+shown+to+express+chemokines%2C+a+group+of+small+molecules+secreted+by+cells+that+induce+chemotaxis+in+responsive+cells%2C+such+as+CCL21%2C+which+is+used+by+CCR7%2B+mature+antigen+presenting+dendritic+cells+(DCs)+to+migrate+to+draining+lymph+nodes+(LNs).+These+previous+findings+indicate+that+LECs+might+play+an+integral+role+in+innate+immune+responses+to+a+wide+variety+of+microbes.+In+this+study%2C+I+set+out+to+characterize+the+expression+of+antiviral+restriction+factors+as+well+as+possible+viral+entry+receptors+for+SIV%2FHIV-1+within+three+populations+of+human+LECs.+Real-time+RT-PCR+and+immunofluorescent+staining+techniques+were+used+to+determine+the+relative+expression+of+the+restriction+factors+BST-2%2FTetherin%2C+APOBEC3G%2C+and+TRIM5-%C3%A1.+All+of+these+factors+have+been+shown+to+inhibit+the+replicative+cycle+of+HIV-1+and+have+othologs+present+in+nonhuman+primates+(NHPs).+Expression+of+the+viral+entry+receptors+CD4%2C+CXCR4%2C+CCR5%2C+DEC-205%2FCD205%2C+D6%2FCCBP2%2C+and+CD209+as+well+as+the+LEC-specific+markers+podoplanin+and+LYVE-1+was+also+investigated.+In+addition%2C+LEC+populations+were+exposed+to+SIV%2C+HIV-1%2C+and+markers+internalization+to+determine+to+what+extent+LECs+interact+with+virus+in+vitro.+Data+from+populations+exposed+to+HIV-1+as+well+as+other+substrates+for+internalization+of+extracellular+materials+illustrate+the+ability+of+LECs+to+actively+monitor+the+extracellular+milieu.+LECs+exposed+to+SIV+showed+multi-spliced+viral+transcripts+possibly+due+to+de+novo+transcription.+Taken+together%2C+this+study+provides+evidence+that+LECs+are+equipped+with+tools+not+only+to+bind+and+internalize+pathogens%2C+but+may+also+serve+as+a+low-level+replicative+cellular+substrate+for+virus.+Further+studies+to+characterize+LECs+are+of+great+public+health+relevance%2C+particularly+at+mucosa+sites+of+microbial+exposure%2C+due+to+their+potential+roles+during+transmission%2Finfection.&rft.date=2011-09-28&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%2F8272%2F1%2FChrisopher_D_Bowen_FINAL.pdf&rft.identifier=++Bowen%2C+Christopher+David++(2011)+Lymphatic+Endothelial+Cells+Express+Viral+Entry+Receptors+and+Restriction+Factors.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++