Title |
Hepatitis B virus (HBV)-Viral Particle Assembly
|
Institution |
BROWN UNIVERSITY, PROVIDENCE, RI
|
Principal Investigator |
KONKIN, TAMAKO
|
NCI Program Director |
H. Aguila
|
Cancer Activity |
Comp Min Biomed Prog
|
Division |
CRCHD
|
Funded Amount |
$26,554
|
Project Dates |
09/01/2006 - 08/31/2009
|
Fiscal Year |
2008
|
Project Type |
Grant
|
Research Topics w/ Percent Relevance |
Cancer Types w/ Percent Relevance |
Cancer (100.0%)
Digestive Diseases (100.0%)
|
Liver Cancer (100.0%)
|
Research Type |
Exogenous Factors in the Origin and Cause of Cancer
|
Abstract |
DESCRIPTION (provided by applicant): HBV chronically infects 400 million people worldwide and increases their risk to develop liver cancer by 100 fold. A unique feature of HBV is the secretion of the small (S) envelope protein as empty "subviral particles" which exceed virions by over 10,000 fold. I hypothesize that the subviral particles suppress the rise of or sequester neutralizing antibodies to prolong viral infection. Alternatively, incorporation of nucleocapsid to the assembly process mediated by the S protein is extremely inefficient, thus requiring S protein overproduction. I will use trans-complementation assay to determine the effect of envelope protein expression level and S/L (large envelope protein) ratio on virion secretion efficiency. Next, I will generate HBV mutants with drastically reduced expression of the envelope proteins and establish their secretion efficiency of viral and subviral particles. If virion secretion is sustained I plan to generate similar duck hepatitis B variants. Whether such variants produce a shorter course of infection than the wild-type virus will be tested in ducks. If virion secretion is impaired, I will determine the feasibility to overcome the defect by incorporation of a novel glycosylation site. Successful completion of this study will solve this long-standing puzzle of medical importance. |