David D. Dunigan, Ph. D.

Research Assistant Professor University of Nebraska-Lincoln Department of Plant Pathology Nebraska Center for Virology 406 Plant Sciences Hall Lincoln, NE 68583-0722 Phone - 402.472.2858 Fax - 402.472.2853 ddunigan2@unl.edu

Research Interests:

Our research is focused on host-virus interactions, especially as it relates to pathogenesis. I have investigated several eukaryotic viral systems, including both plant and animal viruses. In considering virus infections generally, I have searched for common functions and events that tend to unite themes in virology, and these have included the ability of most viruses to capture the cellular machinery for protein and nucleic acid synthesis upon infection. One phenomena observed with many viruses is the rapid shutoff of host-directed macromolecular synthesis, while subverting the machinery and metabolic resources to the production of viral molecules. For RNA viruses, the major advantage is to gain metabolic energy and nucleotide pools, in as much that these viruses tend to encode their own polymerases. In addition to gaining energy and substrate molecules, DNA viruses may take advantage of the host polymerase functions directly, especially those lacking RNA polymerase (e. g., herpesviruses and chlorella viruses), by subverting host RNA polymerase II to transcribe the viral template to make the immediate-early transcripts.

The present work is in collaboration with Dr. James Van Etten, who is a “foundingfather” of the Phycodnavirus family, the type member being Paramecium bursariachlorella virus-1 (PBCV-1). PBCV-1 is well characterized with respect to itslarge dsDNA genome (330 kb) and ~375 open reading frames. The virion is equallyimpressive with respect to size (190 nm diameter icosahedral particle, T = 169)and complexity. Evolutionarily, these viruses are related to other large DNAviruses, such as poxviruses, African swine fever virus, and the iridoviruses.We are investigating the proteome of the virion. Many of the virion-associatedproteins have functions (or putative functions) that suggest the ability to controlhost macromolecular synthesis upon infection. Our current hypothesis is thatvirion-associated proteins are responsible for the immediate-early shutoff ofhost transcription in PBCV-1 infected Chlorella NC64A cells.

Knowledge of how and when viruses gain control of the host cells may lead to novel control methods, including the development of new anti-viral drugs and the mitigation of viral pathogenesis.

Selected Recent Publications:

1. Zhang, Y., Maley, F., Maley, G. F., Duncan, G., Dunigan, D. D., Van Etten, J. L. A bifunctional dCMP-dCTP deaminase encoded by chlorella virus PBCV-1. Journal of Virology 81: 7662-7671, 2007.

2. Agarkova, I., Dunigan, D. D., Van Etten, J. L. Virion-associated restriction endonucleases of chloroviruses. Journal of Virology 80: 8114-8123, 2006

3. Chan, S., Zhu, Z., Dunigan, D. D., Van Etten, J. L., Xu, S. Cloning of Nt.CviQII nicking endonuclease and its cognate methyltransferase: MtCviQII methylates AG sequences. Protein Expression and Purification 49: 138-150, 2006.

4. Dunigan, D. D., Fitzgerald, L. A., Van Etten, J. L. Phycodnaviridae: A peek at genetic diversity. Virus Research 117 (1): 119-132, 2006.

5. Kang, M., Dunigan, D. D., Van Etten, J. L. Chlorovirus: a genus of Phycodnaviridae that infects certain chlorella-like green algae. Molecular Plant Pathology 6 (3): 213-224, 2005.

6. Awada, T., Dunigan, D. D., Dickman, M. B. Animal anti-apoptotic genes enhance recovery from drought stress in tobacco. International Journal of Agriculture & Biology 6: 943-949, 2004.

7. Awada, T., Dunigan, D.D. and Dickman, M.B. Animal anti-apoptotic genes ameliorate the loss of turgor in water-stressed transgenic tobacco. Canadian Journal of Plant Sci. 83: 499-506, 2003.

8. Chen, S., Dunigan, D. D., Dickman, M. B. Bcl-2 family members inhibit oxidative stress-induced programmed cell death in Saccharomyces cerevisiae. Free Radicals in Biology and Medicine 34(10): 1315-1325, 2003.

9. Redman, R. S., Dunigan, D. D., and Rodriguez, R. J. Fungal symbiosis from mutualism to parasitism: who controls the outcome, host or invader?  New Phytologist 151(3): 705-716, 2001.

10. Sweat, J. M., Dunigan, D. D., Wright, S. E. Characterization of kidney epithelial cells from the West Indian manatee Trichechus manatus.  In Vitro Cellular and Developmental Biology-Animal 37 (6): 386-394, 2001.

Recent Selected Abstracts:

D. Dunigan, T. Fangman, Y. Zhou, B. Kronschnabel, I. Agarkova, J. Van Etten.  4th Algal Virus Workshop, held in Amsterdam, The Netherlands, April 2005. Title: “Immediate-early events in PBCV-1 infection of Chlorella NC64A: A confocal laser scanning microscopy analysis”;  D. Dunigan, R. Cerny, L. Fitzgerald, I. Agarkova, B. Kronschnabel, J. Van Etten.Title: “Analyses of three chlorovirus virions”

D. Dunigan, R. Cerny, L. Lane, L. Fitzgerald, I. Agarkova, B. Kronschnabel, and J. Van Etten. Annual Meeting of The American Society for Virology, held at Madison, Wisconsin; July 2006.  Title: “Comparative proteomic analysis of chloroviruses”

D. Dunigan, Garry A. Duncan, Lisa A. Fitzgerald, Michael V. Graves, James R. Gurnon, James L. Van Etten Second Annual Department of Energy-Joint Genome Institute User Meeting, held in Walnut Creek, CA, April 2007. Title (Poster) Comparative genomics of chloroviruses; co-authors:

D. Dunigan, G. Duncan, Y. Zhang, and J. Van Etten. Annual Meeting of The American Society for Virology, held at Corvallis, Oregon; July 2007.  Title: “Chloroviruses augment nucleotide metabolism”

Recent Invited Lectures:

2007
“The life and times of giant viruses”, Nebraska Wesleyan University, Lincoln, Nebraska

“Early events in chlorovirus infections”, University of Nebraska-Lincoln

2006
“In search of the unknowns: Gene discovery using evolutionary genomics”, University of Nebraska-Lincoln

2005
“Immediate-early events in chlorella virus infections”, John Innes Centre, Norwich, United Kingdom

“Host-virus interactions and the consequences of infection”, University of Cambridge, Cambridge, United Kingdom