Development and characterization of an in vitro culture system as a physiological model for chronic Hepatitis B infection

Human Hepatitis B virus (HBV) is the prototype member of the family Hepadnaviridae that consists of enveloped, partially double stranded DNA viruses that specifically target hepatocytes for viral replication. Although a vaccine has been available for more than 20 years chronic HBV infection afflicts 350-400 million worldwide. It is estimated that 0.5-1.2 million people die each year from HBV-attributable cases of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Significant disadvantages exist among currently available therapeutics (e.g. IFNca, lamivudine, adefovir, etc.) that include limited efficacy and the promotion of drug-resistant viral strains. These therapeutics are the research products of the HBV molecular biology that can be manipulated in the laboratory setting. Future antiviral drug therapy is dependent upon the development of better cell culture systems that will allow the study of the complete viral life cycle. The use of primary human and primate hepatocytes is restricted by multiple experimental limitations including a rapid loss of susceptibility to infection in culture, lot-to-lot variability inherent in primary cell culture, and the necessity of treatment with chemical agents such as DMSO for reproducible infection.

Department dc:contributor.department

Massachusetts Institute of Technology. Biological Engineering Division.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Sams, Alexandria V. (Alexandria Victoria)

Advisor dc:contributor.advisor

• Linda G. Griffith.

• Biological Engineering Division.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/39915

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/39915