"Structure of hepadnaviral pre-genomic RNA". [ 2000 - 2001 ]

Research Grant

Researchers: A/Pr Allison Jilbert (Principal investigator)

Brief description Title: Structure of hepadnaviral pre-genomic RNA. We aim to study the replication strategy of human hepatitis B virus (HBV), a member of the hepadnavirus family. Hepadnaviruses infect hepatocytes in the liver and are released in high numbers into the bloodstream. Infection is transmitted by blood or sexual contact. Hepadnaviruses cause acute and chronic infection with varying degrees of liver disease. The HBV DNA genome is formed by copying of a viral pre-genome made of RNA, into DNA. This process is called reverse transcription and is performed by the viral polymerase. Reverse transcription occurs within viral nucleocapsids made of core antigen. After formation of the new viral DNA genome, nucleocapsids are enveloped in surface antigen and are released from the cell. It is assumed that 1 copy of HBV pre-genomic RNA is packaged within each viral nucleocapsid. However, members of the retrovirus family that have common evolutionary origins to hepadnaviruses and also replicate via reverse transcription, contain 2 copies of RNA. The human immunodeficiency virus (HIV), the AIDS virus, is a well-studied example. In HIV infection 2 RNA genomes are packaged into each nucleocapsid and form a dimeric RNA genome. The HIV RNA is able to fold into a series of stem loops that promote formation of dimers. During the reverse transcription step in HIV replication, the polymerase switches templates and forms new combined strains of virus. The project aims to determine if 2 copies of pre-genomic RNA are packaged into HBV nucleocapsids. HBV pre-genomic RNA is able to form stem loop structures similar to those in HIV and has the potential to form dimeric RNA. If 2 copies of HBV pre-genomic RNA are packaged this will allow us to redefine the viral replication strategy and to develop a greater understanding of the relationships between hepadnaviruses and retroviruses. The formation of dimers will also provide a mechanism for recombination between HBV strains.

Funding Amount $AUD 105,866.38

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant