?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%2F12011%2F&rft.title=HIV-1+infection+induced+microRNA+expression+profile+and+its+downstream+effects+on+cellular+transcriptome&rft.creator=Duskova%2C+Karolina&rft.description=HIV-1+infected+individuals+show+a+remarkable+variation+in+virus+replication+and+disease+progression.+Host+cellular+gene+expression+as+a+response+to+virus+infection+is+directly+correlated+with+disease+patterns.+Here%2C+we+examine+the+role+of+microRNAs+on+mRNA+regulation+and+its+effect+in+HIV-1+disease+progression+by+performing+a+comparative+microRNA+and+mRNA+profiling.%0D%0ATotal+RNA+was+extracted+from+subjects+with+high+viral+load+(HVL)(%3E45%2C000+copies%2Fml)%2C+low+viral+load+(LVL)+(~%3C40+copies%2Fml)%2C+and+uninfected+controls.+RNA+was+quality+tested+and+then+reverse+transcribed+and+tested+using+a+Megaplex+Real-time+PCR+for+the+quantification+of+expression+of+754+miRNAs%2C+in+addition+to+controls%2C+using+a+high+throughput+array.+Transcriptome+profiling+was+carried+out+using+Illumina+HT-12+array%2C+which+targets+more+than+28%2C688+annotated+genes+with+more+than+47%2C231+probes.+Computational+analysis+to+find+the+mRNA+targets+of+significantly+differentially+regulated+miRNAs+was+performed+with+the+expression+values+of+both+miRNA+and+mRNA%2C+supplemented+with+a+GenMir%2B%2B.%0D%0AHIV-1+infection+with+high+viral+load+significantly+dysregulated+the+miRNA+profile+in+the+infected+individuals+compared+to+uninfected+or+LVL+group%2C+whereas+infection+with+low+viral+load+produced+a+less+distinctive+profile+compared+to+the+controls.+These+differences+are+independent+of+age+within+these+populations.+Independent+validations+confirmed+the+high+throughput+results+in+65-85%25+in+independent+donors.+GO+enrichment+analysis+further+showed+34+significant+terms%0D%0Aiv%0D%0Aof+biological+processes+in+the+high+viral+load+compared+to+controls.+A+less+distinctive+profile+was+seen+in+the+low+viral+load+samples+compared+to+controls+on+both+the+miRNA+and+mRNA+levels.+Biological+validation+studies+also+confirmed+the+expression+of+HIV+induced+host+cellular+factors+in+in+vitro+infected+samples.+Together%2C+these+results+indicate+that+HIV-1+infection+differentially+regulates+host+cellular+transcriptome+through+miRNA+expression.%0D%0APublic+health+relevance%3A+Viral+load+significantly+upregulates+miRNA+expression%2C+which+translates+to+an+altered+expression+on+the+mRNA+level.+The+discovery+of+microRNAs+that+play+a+role+in+HIV+infection+could+lead+to+the+development+of+new+biomarkers+that+could+be+used+to+identify+disease+progression+within+the+infected+individuals+as+well+as+the+infected+individuals%E2%80%99+ability+to+respond+to+antiviral+treatment.&rft.date=2012-06-29&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%2F12011%2F1%2FDuskovaK_ETD_2012.pdf&rft.identifier=++Duskova%2C+Karolina++(2012)+HIV-1+infection+induced+microRNA+expression+profile+and+its+downstream+effects+on+cellular+transcriptome.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++