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Fusion of Human Serum Albumin to Human Apolipoprotein E Peptide as a Novel Inhibitor of Hepatitis C Virus entry

Deshmukh, Brandon (2012) Fusion of Human Serum Albumin to Human Apolipoprotein E Peptide as a Novel Inhibitor of Hepatitis C Virus entry. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

The hepatitis C virus (HCV) affects an estimated 3% of the world’s population making it a major threat to human health. Currently, the most common treatment for those infected with the virus includes a combination of pegylated interferon (IFN-α) with ribavirin. This treatment is effective only 40-80% of the time and causes severe side effects leading to low patient compliance. In 2011, two anti-HCV drugs, telaprevir and boceprevir, were put on the market. Both of these drugs are viral protease inhibitors, 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, 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, as well as lower plasma cholesterol levels and suppress inflammation in mice. At the same time, this peptide was non-toxic to cells. The combination of potently blocking viral entry, 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, we believed that fusing it to human serum albumin would increase its pharmacokinetics, shelf life, 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-α 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, we saw viral inhibition among one of our hEP fusion proteins, demonstrating its efficacy and public health significance.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Deshmukh, Brandonbad34@pitt.eduBAD34
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee MemberEvans, Jaredevansj2@cvr.pitt.eduEVANSJ2
Committee MemberTarun, Salvadorszt3@pitt.eduSZT3
Thesis AdvisorWang, Tianyitywang@pitt.eduTYWANG
Date: 21 September 2012
Date Type: Publication
Defense Date: 12 June 2012
Approval Date: 21 September 2012
Submission Date: 10 July 2012
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Number of Pages: 75
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: hepatitis c, apolipoprotein E, peptide
Date Deposited: 21 Sep 2012 20:05
Last Modified: 21 Sep 2017 05:15
URI: http://d-scholarship.pitt.edu/id/eprint/12815

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