Variations on the RNA genome of hepatitis delta virus.

Format:

Book

Thesis/Dissertation

Author/Creator:

Wu, Dingding.

Contributor:

Taylor, John M., advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Microbiology.

Molecular biology.

0307.

0410.

Penn dissertations--Cell biology.

Cell biology--Penn dissertations.

Penn dissertations--Molecular biology.

Molecular biology--Penn dissertations.

Local Subjects:

Penn dissertations--Cell biology.

Cell biology--Penn dissertations.

Penn dissertations--Molecular biology.

Molecular biology--Penn dissertations.

0307.

0410.

Physical Description:

165 pages

Contained In:

Dissertation Abstracts International 58-07B.

System Details:

Mode of access: World Wide Web.

text file

Summary:

Hepatitis delta virus (HDV) is a subviral satellite of hepatitis B virus. The unique HDV genome is a single-stranded circular RNA of 1679 nucleotides and can fold into an unbranched rodlike structure with 70% of the nucleotides base-paired. The aims of this research were to investigate (i) the stability of the HDV genome, (ii) the editing mechanism which modifies HDV RNA during the replication cycle, and (iii) the cis-acting sequences by mutagenesis of HDV RNA.

To study the stability of the HDV genome, the infection was initiated with a single sequence by assembling HDV virions in cultured cells. After serial passages of HDV in animals, liver RNA was extracted for analyzing a specific 352-nucleotide region of the HDV genome. In addition to the essential U to C change at nucleotide 1012, the majority of the other detected changes on the genome, might be attributed to the same post-transcriptional RNA editing that generates the change at nucleotide 1012. It was also found that the editing could occur at an experimentally created site at nucleotide 1011, adjacent to the normal editing site, nucleotide 1012. The above results are consistent with double-stranded RNA adenosine deaminase being the enzyme responsible for most of the nucleotide changes on HDV RNA.

Deliberate mutations were introduced at two ends of the rodlike HDV RNA and assayed for the effects on the ability of the genomes to replicate and accumulate RNA in transfected cells. Most mutations at the top end, defined as that nearest to the 5$\sp\prime$-end of mRNA, had inhibitory effects. Some of the top mutants could be partially rescued by providing the small delta antigen in trans, indicating that certain features at the top might be needed for the accumulation of essential delta antigen mRNA species. In contrast, most mutations at the bottom end were tolerated. Consistent with the potential of HDV to act as a vector, in one mutant altered at the bottom, 13 nucleotides of HDV sequence were replaced with 57 nucleotides of non-HDV sequences and RNA accumulation was at 20% relative to wild type.

Notes:

Thesis (Ph.D. in Cell and Molecular Biology) -- University of Pennsylvania, 1997.

Source: Dissertation Abstracts International, Volume: 58-07, Section: B, page: 3485.

Supervisor: John M. Taylor.

Local Notes:

School code: 0175.

ISBN:

9780591502077

Access Restriction:

Restricted for use by site license.