RNAIG - MEMBERS: John L. Casey, Ph.D.

John L. Casey, Ph.D.
Division of Molecular Virology
Georgetown University Medical Center
5640 Fishers Lane
Phone (301) 881-2676 ext 26
Fax (301) 881-0810
caseyj@medlib.georgetown.edu

RESEARCH INTERESTS

[Hepatitis Delta Virus] [(HDV)] is a sub-viral human pathogen that causes severe acute and chronic liver disease. The genome of HDV is a 1680nt single-stranded circular RNA which<shares some functional and structural similarities with plant viroid and virusoid agents. Our work is directed at understanding the mechanisms of HDV replication and pathogenesis by investigations at the molecular level and in the natural setting. Much of our effort has been devoted to study of an [RNA editing] event that is central to the virus life cycle (1,3). In earlier work we defined RNA<structural elements required for editing. More recently we have identified the antigenomic RNA<of HDV as the substrate for editing both in vivo and in vitro, leading to the suggestion that a ubiquitous cellular enzyme, [double-stranded RNA<adenosine deaminase] (also [dsRAD] or [DRADA]), is responsible for HDV RNA<editing. Current work in this area is directed at confirming this hypothesis (in collaboration with Brenda Bass and her group), and on exploring the regulation of editing in vivo and in vitro. We are also examining the role of editing in both naturally occurring infections and in animal models of HDV disease.

As part of our analysis of HDV disease, we have obtained the sequence of numerous HDV isolates from many areas of the world and have defined 3 HDV genotypes (2). We have found that [genotype] I is prevalent in most areas of the world, but that genotype III is unique to northern South America, where patterns of HDV-related disease are particularly severe. Clones of HDV genotype III are being analyzed and compared with genotype I clones, both in cultured cells and in animal models of HDV disease. Additional work is directed at evaluating the stability of the genome in model systems (genetic drift might be related to pnon-specificz editing events, perhaps by dsRAD).

PUBLICATIONS

1. Casey JL, Bergmann KF, Brown TL, Gerin JL. Structural requirements for RNA editing in hepatitis delta virus: evidence for a uridine-to-cytidine editing mechanism. Proc Natl Acad Sci U S A. 89 (15): 7149-53. 1992.
   
   
2. Casey JL, Brown TL, Colan EJ, Wignall FS, Gerin JL. A genotype of hepatitis D virus that occurs in northern South America. Proc Natl Acad Sci U S A. 90 (19): 9016-20. 1993.
   
   
3. Casey JL and Gerin JL. Hepatitis D Virus RNA Editing: Specific Modification of Adenosine in the Antigenomic RNA. J. Virol. 1995 (in press).
   
   

LABORATORY MEMBERS

John L. Casey, Ph.D. caseyj@medlib.georgetown.edu
John L. Gerin, Ph.D. (Division head)
Thomas L. Brown, M.S.

INQUIRIES should be sent to:

John L. Casey
Division of Molecular Virology
Georgetown University Medical Center
Rockville, MD 20852
Phone: (301) 881-2676
Fax: (301) 881-0810
email caseyj@medlib.georgetown.edu