?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%2F12815%2F&rft.title=Fusion+of+Human+Serum+Albumin+to+Human+Apolipoprotein+E+Peptide+as+a+Novel+Inhibitor+of+Hepatitis+C+Virus+entry&rft.creator=Deshmukh%2C+Brandon&rft.description=The+hepatitis+C+virus+(HCV)+affects+an+estimated+3%25+of+the+world%E2%80%99s+population+making+it+a+major+threat+to+human+health.++Currently%2C+the+most+common+treatment+for+those+infected+with+the+virus+includes+a+combination+of+pegylated+interferon+(IFN-%CE%B1)+with+ribavirin.++This+treatment+is+effective+only+40-80%25+of+the+time+and+causes+severe+side+effects+leading+to+low+patient+compliance.++In+2011%2C+two+anti-HCV+drugs%2C+telaprevir+and+boceprevir%2C+were+put+on+the+market.++Both+of+these+drugs+are+viral+protease+inhibitors%2C+and+are+expected+to+face+drug+resistance+in+the+future+due+to+the+development+of+viral+quasispecies.++Due+to+the+uncertainty+and+problems+the+current+HCV+treatments+face%2C+there+is+an+urgent+need+to+develop+more+effective+anti-HCV+therapies.++The+blocking+of+HCV+entry+into+human+hepatocytes+has+promise.++Our+lab+has+already+developed+a+novel+anti-HCV+peptide+called+human+apolipoprotein+E+peptide+(hEP)+which+was+shown+to+potently+block+HCV+entry+into+Huh7.5.1+cells+at+very+low+concentrations%2C+as+well+as+lower+plasma+cholesterol+levels+and+suppress+inflammation+in+mice.++At+the+same+time%2C+this+peptide+was+non-toxic+to+cells.++The+combination+of+potently+blocking+viral+entry%2C+as+well+as+maintaining+the+integrity+of+the+cells+treated+makes+hEP+a+promising+anti-HCV+therapeutic.++In+order+to+increase+the+stability+of+hEP%2C+we+believed+that+fusing+it+to+human+serum+albumin+would+increase+its+pharmacokinetics%2C+shelf+life%2C+as+well+as+lower+the+necessary+dosage+needed+to+elicit+anti-viral+effects.++This+rationale+was+based+on+the+findings+of+another+group+which+showed+that+the+fusion+of+IFN-%CE%B1+to+human+serum+albumin+increased+its+half-life.++The+methylotropic+yeast+strain+X-33+Pichia+pastoris+was+used+to+produce+the+hEP+and+human+serum+albumin+recombinant+fusion+protein.++After+successfully+producing+the+recombinant+proteins+of+interest%2C+we+saw+viral+inhibition+among+one+of+our+hEP+fusion+proteins%2C+demonstrating+its+efficacy+and+public+health+significance.&rft.date=2012-09-21&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%2F12815%2F1%2FBrandon_Deshmukh_Thesis.pdf&rft.identifier=++Deshmukh%2C+Brandon++(2012)+Fusion+of+Human+Serum+Albumin+to+Human+Apolipoprotein+E+Peptide+as+a+Novel+Inhibitor+of+Hepatitis+C+Virus+entry.++Master's+Thesis%2C+University+of+Pittsburgh.++++(Unpublished)++