University at Buffalo
The Witebsky Center

The Witebsky Center
University at Buffalo
Bacteriology hostmicrobe immunology parasitology virology bioinformatics mycology
The Witebsky Center The Witebsky Center
William Ruyechan, Ph.D.

Virology Faculty:
John Hay, Ph.D., Amy Jacobs, Ph.D., Thomas Melendy, Ph.D., Edward G. Niles, Ph.D., William T. Ruyechan, Ph.D.


William T. Ruyechan, Ph.D. Professor
Department of Microbiology & Immunology

It is with great sorrow that we inform our members, colleagues, friends, and families of the passing of Dr. Bill Ruyechan on Aug. 15, 2011 after a long term illness.  Bill was one of the founding members of the Witebsky Center for Microbial Pathogenesis and Immunology and served as one of the first Directors of the Center.  He will be greatly missed by all of us.  

Click here to link to Dr. Ruyechan's Memorial

Replication and Expression of Viral and Trypanosomatid Genomes

My research interests center on molecular biology and pathogenesis in three different biological systems: herpes simplex virus (HSV), varicella zoster virus (VZV) and the parasitic protozoan Trypanosoma brucei. The work with HSV involves functional analysis of the HSV major DNA-binding protein. We are presently mapping important regions of the protein by means of chemical modification, photo-crosslinking, and expression of fragments in prokaryotic vector systems. The regions being analyzed include the DNA-binding domain, a zinc binding site, and a region of the protein involved in cooperative binding. We have generated site specific mutations at or near the residues involved in cooperative binding and are analyzing the effects of these mutations on viral DNA replication. The work on varicella zoster virus is focused on VZV gene regulation and the molecular mechanisms required for the establishment and maintenance of VZV latency. We are currently determining the mechanism involved in the cell type specific modulation of VZV transcriptional activation of the viral glycoprotein I promoter and a novel bi-directional promoter regulating expression of two important DNA replication functions. This phenomenon involves gene products which are present both during lytic and latent viral infection. We have also shown that two ubiquitous transcription factors, USF and Sp1, are required for activation of the gI promoter. Expression of correct levels of glycoprotein I are required for efficient cell-to cell spread of the virus and pathogenesis in skin and T cells.  In collaboration with Dr. Noreen Williams, a novel DNA polymerase and two RNA-binding proteins have been identified in T. brucei. The expression of the latter two proteins is developmentally regulated during the life cycle of the parasite and they are associated with 5SRNA. The Rna-binding proteins are novel to trypanosomes and appear to be involved in various aspects of RNA metabolism and gene regulation.

 

Recent Publications:

Ito, H., Sommer, M. H., Zerboni, L., He, Hongying, Boucaud, D., Hay, J., Ruyechan, W. and Arvin, A. M. Promoter sequences of varicella-zoster virus glycoprotein I targeted by cellular transcription factors Sp1 and USF determine virulence in skin and T cells in SCIDhu mice in vivo. J. Virol.77: 489-498, 2003.

Ruyechan, W. T., Peng, H., Yang, M. and Hay, J. Cellular factors and IE62 activation of VZV promoters. J. Med. Virol.70: S90-S94, 2003.

Van Oss, C. J., Giese, R. F., Bronson, P. M., Docoslis, A., Edwards, P., and Ruyechan, W. T. Macroscopic-scale surface properties of streptavidin and their influence on aspecific interactions between streptavidin and dissolved biopolymers. Colloids and Surfaces-B: Biointerfaces 30: 25-36, 2003.

Li, J., Ruyechan, W. T., and Williams, N. Stage specific translational efficiency and protein stability regulate the developmental expression of p37, an RNA-binding protein from T. brucei. Biochem. Biophys. Res. Comm. 306: 918-923, 2003.

Peng, H., He, H., Hay, J., and Ruyechan, W. T. Interaction between the varicella zoster virus IE62 major transactivator and cellular transcription factor Sp1. J. Biol. Chem. 278: 38068-38075, 2003.

Rahaus, M., Desloges, N., Yang, M., Ruyechan, W. T., and Wolff, M. H. Transcription factor USF, expressed during the entire phase of VZV infection, interacts physically with the major viral transactivator IE62 and plays a significant role in virus replication. J. Gen. Virol.84: 2957-2967, 2003

Duhagon, M.A., Dallogiovanna, B., Ciganda, M., Ruyechan, W., Williams, N., and Garat, B. A novel type of single-stranded nucleic acid binding protein recognizing a highly frequent motif in the intergenic regions of Trypanosoma cruzi. Biochem. Biophys. Res. Commun. 309: 183-188, 2003.

Baiker, A.., Bagowski, C., Ito, H., Sommer, M., Fabel, K., Hay, J., Ruyechan, W., and Arvin, A. The immediate early 63 protein of varicella zoster virus: analysis of functional domains required for replication in vitro and for T-cell and skin tropism in the SCIDhu model in vivo. J. Virol. 78: 1181-1194, 2004.

Grose, C., Tyler, S., Peters, G., Hiebert, J., Stephens, G. M, Ruyechan, W. T.., Jackson, W., Storlie, J., and Tipples, G. A.. Complete DNA sequence analysis of the first two gE (D150N) VZV mutant viruses found in North America: evolution of genotypes with an accelerated cell spread phenotype. J. Virol. 78: 6799-6807, 2004.

Yang, M., Hay, J., and Ruyechan, W. T. The DNA element controlling expression of the varicella zoster virus ORF 28 and ORF 29 genes consists of two divergent unidirectional promoters which share a common USF site. J. Virol. 78: 10939-10952, 2004.

Ruyechan, W. T. Mechanism(s) of Activation of Varicella Zoster Virus Promoters by the VZV IE62 Protein, Recent Research Developments in Virology 6: 145-172, 2004.

Narayanan, A., Nogueira, M. L., Ruyechan, W. T., and Kristie, T. M. Combinatorial transcription of the HSV and VZV IE genes is strictly determined by the cellular coactivator HCF-1. J. Biol. Chem. 280: 1369-1375, 2005.

Ito, H., Sommer, M. H., Zerboni, L., Baiker, A., Sato, B., Liang, R., Hay, J., Ruyechan, W. T., and Arvin, A. M. The role of the varicella-zoster virus gene product encoded by open reading frame 35 in viral replication in vitro and in differentiated human skin and T cells in vivo. J. Virol. 79: 4819-4827, 2005

Zuranski, T., Nawar, H., Czechowski, D., Lynch, J. M., Arvin, A. M., Hay, J., and Ruyechan, W. T. Cell type dependent activation of the cellular EF-1α promoter by the varicella zoster virus IE63 protein. Virology. 338: 35-42, 2005

Narayanan, A., Nogueira, M. L., Ruyechan, W. T., and Kristie, T. M. Combinatorial transcription of the HSV and VZV IE genes is strictly determined by the cellular coactivator HCF-1. J. Biol. Chem. 280: 1369-1375, 2005.

Ito, H., Sommer, M. H., Zerboni, L., Baiker, A., Sato, B., Liang, R., Hay, J., Ruyechan, W. T., and Arvin, A. M. The role of the varicella-zoster virus gene product encoded by open reading frame 35 in viral replication in vitro and in differentiated human skin and T cells in vivo. J. Virol. 79: 4819-4827, 2005

Yang, M., Peng, H., Hay, J., and Ruyechan, W. T.  Promoter Activation by the Varicella Zoster Virus Major Transactivator and the Cellular Transcription Factor USF. J. Virol. 80: 7339-7353, 2006.

Hamza, M. A., Higgins, D. M., and Ruyechan, W.T. Herpes Simplex Virus Type‑1 Latency Inhibits Dendritic Growth in Sympathetic Neurons, Neurobiol. Dis. 24: 367-373, 2006.

Cillioniz, C., Jackson, W., Grose, C., Czechowski, D., Hay, J., and Ruyechan, W. T.  The Varicella Zoster Virus ORF9 Protein Interacts with the IE62 Major VZV Transactivator. J. Virol. 81: 761-774, 2007.

Hamza, M. A., Higgins, D. M., and Ruyechan, W.T. Two Alphaherpesvirus Latency-Associated Gene Products Influence Calcitonin Gene-Related Peptide Levels in Rat Trigeminal Neurons. Neurobiol. Dis. 25: 553-560, 2007.

Hamza, M. A., Higgins, D. M., and Ruyechan, W.T. Herpes simplex Type 1 Latency-Associated Transcript-induced Immunoreactivity of Substance P in Trigeninal Neurons is Reversed by Bone Morphogenic Protein. Neuroscience Letters, 413: 31-35, 2007.

Che, X., Berarducci, B., Sommer, M., Ruyechan, W. T., and Arvin, A. M. The Ubiquitous Cellular Transcription Factor, USF, Targets the Varicella-Zoster Virus ORF10 Promoter and Determines Virulence in Human Skin Xenografts in SCIDhu Mice In Vivo. J. Virol. 81: 3229-3239, 2007.

Hamza, M., Higgins, D. M., Feldman, L. J., and Ruyechan, W. T. The Latency-Associated Transcript of Herpes Simplex Virus Type-1 Promotes Survival and Stimulates Axonal Regeneration in Sympathetic and Trigeminal Neurons. J. Neurovirol. 13: 56-66, 2007.

Narayanan, A., Ruyechan, W. T., and Kristie, T. M. The Coactivator HCF-1 Mediates Set1 and MLL1 H3K4 Trimethylation of Herpesvirus IE Promoters for Initiation of Infection. Proc. Nat’l. Acad. Sci. USA (In Press) 2007.

Hamza MA. Higgins DM. Ruyechan WT. Herpes simplex virus type-1 latency inhibits dendritic growth in sympathetic neurons. Neurobiology of Disease. 24(2):367-73,. 2006 Nov.

Hamza MA. Higgins DM. Feldman LT. Ruyechan WT. The latency-associated transcript of herpes simplex virus type 1 promotes survival and stimulates axonal regeneration in sympathetic and trigeminal neurons. Journal of Neurovirology. 13(1):56-66, 2007.

 

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