QUANTIFICATION OF GENOME PACKAGING IN HBV NUCLEOCAPSIDS

Stanford University, Stanford CA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This research aims to provide experimental data in support of experimental and theoretical approaches for predicting non-specific biomolecular interactions within Hepatitis B virus (HBV) nucleocapsids that underpin the viral capsid formation and stability. Small-angle x-ray scattering measurements will be carried out on mature, pregenomic and empty nucleocapsids. These will be used synergistically and iteratively with modeling to provide for data interpretation and model optimization and verification. The proposed research aims to solve the internal microscopic structure of nucleocapsids including the distributions of encapsidated nucleic acids and unstructured protein domains and provide a basis to understand viral assembly. The first measurements will provide a base line for later scattering experiments and modeling on nucleocapsids, biochemicaly and genetically modified nucleocapsids to provide information on HBV morphogenesis. The scattering and theoretical analysis will in turn frame future biochemical and genetic approaches to regulate and ultimately eradicate HBV infection.