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Title: Determinants of Hepatitis B and delta viral host tropism and pathogenesis
Authors: Winer, Benjamin Yana
Advisors: Plus, Alexander
Contributors: Molecular Biology Department
Keywords: genetically humanized mice
Hepatitis B virus
Hepatitis delta virus
human liver chimeric mice
Non-human primates
Subjects: Virology
Cellular biology
Issue Date: 2019
Publisher: Princeton, NJ : Princeton University
Abstract: Hepatitis B virus (HBV) is an ancient virus that has been one of the most persistent and successful in human history. Globally, two billion people have been infected with HBV, with approximately 257 million becoming chronically infected, resulting in around one million deaths a year. Of these chronic HBV carriers, an estimated 15-70 million are co-infected with hepatitis delta virus (HDV), a satellite virus that requires an HBV co-infection as it utilizes the HBV envelope proteins for virion packaging. HBV/HDV co-infections are the most severe form of viral hepatitis. Although there is an efficacious vaccine that protects against infection with both viruses and antiviral treatments that are able to suppress viremia and extend a patient’s life, there is no cure. As such, the global health burden is enormous, with an estimated cost upwards of $20 billion a year. A major hinderance to finding a curative therapy is the limited cellular and host tropism of HBV and HDV as they only robustly infect human and chimpanzee hepatocytes. There is a lack of in vitro culturing systems that can faithfully recapitulate the complex biology of the human liver. In addition, with the moratorium on the use of chimpanzees for federally funded research, there is a dearth of animal models to study HBV and HBV/HDV infections. Novel in vitro culture systems and small animal models are thus desperately needed in order to propel the HBV field forward to understand more about these mysterious viruses and to work towards curative therapies. My thesis work has focused on developing both novel in vitro and in vivo platforms to learn more about the viral life cycle and the host response to infection. I have taken an approach of either adapting non-permissive hosts in order to make them susceptible to HBV and/or HBV/HDV infection or to adapt the virus to infect previously non-permissive hosts. These tools are in and of themselves useful but I went beyond just development and utilized them to gain new insights into the host factors responsible for these viruses’ limited tropism, viral pathogenesis and, most importantly, the host response to infection.
Alternate format: The Mudd Manuscript Library retains one bound copy of each dissertation. Search for these copies in the library's main catalog:
Type of Material: Academic dissertations (Ph.D.)
Language: en
Appears in Collections:Molecular Biology

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