Hepatitis B virus (HBV) is a major cause of morbidity and mortality, worldwide. About 350 million people suffer from chronic HBV and about 600,000 die from its sequellae annually. HBV is an enveloped virus with an icosahedral core that also functions as a metabolic compartment. Indeed, the core protein plays pleiotropic roles in many elements of HBV replication. To accomplish multiple functions we hypothesize a complex allosteric regulation of the protein and the assembled core. We will study assembly of empty cores and correlate that with assembly of cores on nucleic acid substrates. We will examine assembly of cores on nucleic acid substrates and correlate that with reverse transcription. Our preliminary data indicates that the core plays an active role in reverse transcription;it is much more than a passive container. We will correlate the synergism between core structure and reverse transcription with intracellular localization of core. By emphasizing the structural basis f these correlations, we will define the mechanisms relating assembly, reverse transcription of viral RNA, and core trafficking within a cell. In the last few years, the HBV core protein has emerged as a target for antiviral therapeutics. The studies described in our proposal will serve as a basis for defining molecular mechanisms of such antiviral molecules.

Public Health Relevance

Hepatitis B virus is a major cause of morbidity and mortality, worldwide: about 350 million people suffer from chronic HBV and about 600,000 die from it annually. We will investigate the roles HBV core protein plays in the virus replicative cycle. Core protein is emerging as an important antiviral target, making its activities of critical importance or defining antiviral mechanisms.

Agency
National Institute of Health (NIH)
Type
High Priority, Short Term Project Award (R56)
Project #
2R56AI077688-06
Application #
8880573
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Koshy, Rajen
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Indiana University Bloomington
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Bloomington
State
IN
Country
United States
Zip Code
47401