Hepatitis C is a liver disease caused by hepatitis C virus (HCV). HCV is the major cause of cirrhosis and hepatocellular cancer in the US and is the number one cause of liver transplantation. An estimate of 3.5 million people is chronically infected in the US with 400,000 individuals deaths from chronic HCV infection every year. Several direct-acting antiviral (DAA) agents have been approved by the Food and Drug Administration (FDA). HCV is a blood-borne virus, which prior to 1992 was transmitted through blood transfusion. An estimated 41,200 new cases of HCV infection occurred in the US with an additional 1.75 million worldwide in 2016. Therefore, there is an urgent need to control the transmission of HCV, in addition to the antiviral intervention to limit the spread of the virus. Vaccination is the most effective way to control the infection rate as no infectious disease has ever been eradicated by treatment alone. However, no vaccine is available to prevent HCV infection.
A useful mammalian cell expression system was described to produce HCV envelope glycoproteins E1 and E2, as well as the cell surface receptors, scavenger receptor class B type I (SRB1) and cluster of differentiation 81 (CD81). Our method combines the speed and high efficiency of lentiviral infection with an adherent cell bioreactor to allow large-scale production of proteins in mammalian cell lines. The full-length ectodomain of HCV E1 was produced at milligram quantity and is recognized by conformational antibodies from patient samples. E1 can associate with the apolipoproteins from the cell culture serum. HCV E2 produced by the mammalian cell expression system has the function to bind cell surface receptors and antibodies. Crystals of E2 and CD81 diffract to 4.3 Å resolution allowing us to produce a low-resolution model of the E2-receptor complex.
Overall, our result extends the current understanding of HCV entry by providing more structural, biophysical, and functional information on the HCV glycoproteins. The studies of the receptor interaction can contribute to vaccine design to halt the spread of HCV infection.
Subject (authority = RUETD)
Topic
Chemistry and Chemical Biology
Subject (authority = ETD-LCSH)
Topic
Hepatitis C virus--Treatment
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_9447
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (110 pages) : illustrations
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Yuanyuan Wang
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.