Theo Dreher

Molecular Plant Virology, Transfer RNA

Research

Functions of the 5´ and 3´ untranslated regions of Positive Strand RNA Viruses

Positive strand RNA viruses form a large group of viruses that infect humans (e.g., poliovirus, West Nile virus, hepatitis C virus), animals (e.g., foot and mouth disease virus) and plants (e.g., tobacco mosaic virus). The replication strategies of all members of this group share characteristic similarities, whose understanding may lead to new antiviral strategies. Our studies with these viruses encompass the plant virus, turnip yellow mosaic virus (TYMV), and the human pathogen flaviviruses, dengue virus and West Nile virus. Our common interest with these viruses is in understanding the roles of the 5' and 3' untranslated regions (UTRs) of the genome in directing viral protein synthesis (gene expression) and genome replication. These studies are relevant to understanding ribosome behavior and to vaccine design for flaviviruses.

Initiation coupling and gene expression from embedded ORFs

Our studies with TYMV have revealed a novel form of translational expression, termed initiation coupling, a special variant of leaky scanning. When a second AUG closely follows the primary AUG initiation site of an mRNA, ribosome access to the downstream site is facilitated. Eukaryotic messenger RNAs are thus able to robustly express two polypeptides. We are investigating whether this phenomenon contributes to the expression of the proteome in plants and mammals.

Virus assembly and nanoscience applications

TYMV infections produce filled infectious virions as well as near-empty capsids. The capsid is a protein shell built of 180 copies of the 20-kDa coat protein. This 28 nm icosahedral structure has promising properties that could allow exploitation for encasing molecules with biomedical or engineering applications. We are interested in modifying the capsid to learn about its role in the infection process (virion assembly as well as dis-encapsidation) and to explore nanoscience applications.

Genetic diversity of freshwater cyanobacterial blooms

Every summer, multiple lakes and reservoirs in Oregon and the Pacific Northwest suffer choking blue-green algal (cyanobacterial) blooms, typically caused by the genera Microcystis, Anabaena, Aphanizomenon, Oscillatoria, or Gloeotrichia. Several of these are potentially toxic due to the production of liver or neuro toxins. Recreational access to water bodies can be restricted for months, and cyanobacterial toxin contamination of drinking water is an issue of increasing concern.

We are surveying cyanobacterial blooms from the Klamath River basin and several water bodies in Oregon to genetically characterize the cyanobacterial populations. Genetic identification is addressing inaccuracies in microscopic identification and should allow early warning determination of the potential for toxin production as a bloom develops. In the longer term, we are interested in exploring cyanophages (viruses) as biological control agents.

SELECTED PUBLICATIONS

Pub Med

Matsuda, D and Dreher, T.W.  (2006)  Close spacing of AUG initiation codons confers dicistronic character on a eukaryotic mRNA. RNA 12:1338-49.

Cho, T.-J. and Dreher, T. W. (2006) Encapsidation of genomic but not subgenomic Turnip Yellow Mosaic Virus RNA by coat protein provided in trans.  Virology, in press.
 
Matsuda, D. and Dreher, T. W.  (2006)  Cap- and initiator tRNA-dependent initiation of TYMV polyprotein synthesis by ribosomes: Evaluation of the Trojan horse model for TYMV RNA translation. RNA, in press.

Chiu, W.-W., Kinney, R. M. and Dreher, T. W. (2005) Control of translation by the 5´ and 3´ terminal regions of the dengue virus genome. J. Virol., 79:8303-15.

Kinney, R. M., Huang, C. Y.H., Rose, B. C., Kroeker, A. D., Dreher, T. W., Iversen, P. L. and Stein, D. A. (2005) Inhibition of dengue virus serotypes 1 to 4 in cero cell culture with morpholino oligomers. J. Virol. 79:5116-5128.

Dreher, T. W. (2004) Pathogen profile. Turnip yellow mosaic virus: transfer RNA mimicry, chloroplasts and a C-rich genome. Molecular Plant Pathology 5:367-375.

Matsuda, D., Bauer, L., Tinnesand, K. and Dreher, T. W. (2004) Expression of the two nested overlapping reading frames of TYMV RNA is enhanced by a 5´-cap and by 5´ and 3´ viral sequences. J. Virology 78:9325-9335.

Matsuda, D., Yoshinari, S. and Dreher, T. W. (2004) eEF1A binding to aminoacylated viral RNA represses minus strand synthesis by TYMV RNA-dependent RNA polymerase. Virology 321:47-56.

Matsuda, D. and Dreher, T. W. (2004) The tRNA-like structure of Turnip yellow mosaic virus RNA is a 3´-translational enhancer. Virology 321:36-46.