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
John Hay, Ph.D.

Virology Faculty:
John Hay, Ph.D., Amy Jacobs, Ph.D., Thomas Melendy, Ph.D., Christine O'Connor, Ph.D.

John Hay, Ph.D.
Department of Microbiology & Immunology
Phone: (716) 829-2907
Fax: (716) 829-2158
John Hay

Genetic and Biochemical Dissection of Virus Pathogenesis

 1.      Varicella zoster virus (VZV)

 This human virus causes chickenpox and shingles, but we have no clear idea of the mechanisms through which disease is caused. Our work focuses on a molecular approach to these mechanisms. In collaboration with colleagues at Stanford and Iowa, we have developed a SCIDhu mouse model to assess the virulence of VZV.  We have shown that mutants defective in glycoprotein C and in the ORF47 kinase are essentially non-virulent.  We will be constructing additional mutants based on our work with gene regulatory  proteins, particularly IE62 and IE63.  The long-term goal of the project is to develop a second generation VZV vaccine. 

2.      Chronic Fatigue Syndrome (CFS)

This is a debilitating disease that adversely affects perhaps 5% of the US population. At present there is no evidence to suggest a specific cause for the disease. We have investigated the possibility that certain lymphotropic human viruses may be involved, and shown that neither HHV-6 nor HHV-7 appear to be direct candidates.  We have recently started to  work with Dr. Eng Tan at the Scripps Institute on the possibility that CFS is an autoimmune disease.  Current evidence suggests that an unusual form of antinuclear antibodies may be involved

Recent Publications: 

Natelson, B., LaManca, J., Denny, T., Vladutiu, A., Oleske, J., Hill, N., Bergen., Korn, L. and Hay, J. Immunological function in chronic fatigue syndrome, major depression and multiple sclerosis. Am. J. Med.105: 7S-10S, 1998.

Boucaud, D., Yoshitake, H., Hay, J. and Ruyechan, W.T. The VZV ORF29 protein acts as a modulator of expression of a late VZV protein. J. Inf. Dis. 178, 534-538, 1998.

Ruyechan, W.T. and Hay, J. Varicella zoster virus: molecular biology. In "Encyclopedia of Virology" 2nd Ed. Pp1878-1884. Academic Press, London, 1999.

Wallace, H., Natelson, B., Gause, W. and Hay, J. Human herpesviruses in chronic fatigue syndrome. Clin. Diag. Lab. Immunol. 6, 216-223, 1999.

Teach, S.J., Wallace, H., Evans, M.J., Duffner, P.K., Hay, J. and Faden, H. HHV-6 and HHV-7 in children with febrile convulsions. Pediatric Neurol. 21, 699-703, 1999.

Applegate, K.L., Hay, J., Cacioppo, J.T., Kiecolt-Claser, J.K. and Glaser, R. "The effects of stress on the immune system – implications for reactivation of latent herpesviruses" in Psychoneuroimmunology pp517-524 An Interdisciplinary Introduction. Eds. Schledowski M., Tewes, U. Academic/Plenum New York. 1999.

Spengler, M., Ruyechan, W.T. and Hay, J. Physical interaction between two VZV gene regulatory proteins, IE4 and IE62. Virology, 272, 375-381. 2000.

Santos, R., Hatfield, C., Faga, B., Padilla, J., Cole, N., Moffat, J., Arvin, A., Spengler, M., Ruyechan, W.T., Hay, J. and Grose, C. J. VZV gE escape mutant VZV-MSP exhibits a novel genotype with an accelerated cell-to-cell spread in both infected and SCIDhu mice. Virology, 275, 306-317. 2000.

Ruyechan, W.T. and Hay, J. "VZV DNA replication" in Varicella Zoster Virus. Eds. Arvin, A. and Gershon, Cambridge University Press, Cambridge, pp51-73, 2001.

Spengler, M., Niesen, N., Grose, C., Ruyechan, W.T. and Hay, J. Interactions among structural proteins of VZV. Arch. Virol., 17S, 71-80, 2001.

He, H., Boucaud, D., Hay, J. and Ruyechan, W.T. Cis and trans elements regulating expression of the VZV gI gene. Arch. Virol. 17S, 57-70, 2001.

Sommer, M.H., Zagha, E., Serrano, O.K., Ku, C.C., Hatfield, C., Grose, C., Spengler, M., Ruyechan, W.T., Hay, J. and Arvin, A.M. Mutational analysis of VZV ORF63/70 and ORF64/69. J. Virol., 75, 8224-8239, 2001.

Hay, J., Beutner, E. and Natelson, B. Immune parameters in Chronic Fatigue Syndrome. Recent Advances in Molecular Biology, Allergy and Immunology. 2002, in press.

He, H., Kantakamalakul, W., Hay, J. and Ruyechan, W.T. Analaysis of the activating upstream sequence (AUS) in the VZV gI promoter. Submitted, 2002.

Boucaud, D., Sommer, M., Arvin, A.M., Hay, J. and Ruyechan, W.T.. The VZV ORF29 protein; its role as modulator of viral transcription. Submitted, 2002.

Kenyon, T.K., Lynch, J., Hay, J., Ruyechan, W. and Grose, C. VZV ORF47 protein kinase: characterization of a cloned biologically active phosphotransferase. J. Virol., 75 , 8854-8858, 2001

Arvin, A., Sharp, M., Moir, M., Kinchington, P., Sadeghi-Zadehi, M., Ruyechan, W. and Hay, J. Recognition of the major gE glycoprotein, and tegument and replication proteins of VZV by memory cytotoxic T-cells. 2002, submitted.

Hya, J., Beutner, E. and Natelson, B. Immune parameters in Chronic Fatigue Syndrome. In "Recent Advances in Molecular Biology, Allergy and Immunology" Eds. Ramcand, C.N., Nair, M.N.P, Pilo, B. Allied Publishers Ltd. New Delhi. Pp159-163. 2002.

Ruyechan, W., Peng, H., Yang, M. and Hay, J. Cellular factors and IE62 activation of VZV promoters. J. Med. Virol. 70, S90-94, 2003.

Ito, H., Sommer, M., Zerboni, L., He, H., Boucaud, D., Hay, J., Ruyechan, W and Arvin, A. Promoter sequences of VZV gI targeted by cellular transcription factors Sp1 and USF determine virulence for human skin and T-cells in the SCIDhu mouse. J. Virol., 77, 489-498, 2003

Peng, H., He, H., Hay, J. and Ruyechan, W.T. Interaction between the VZV IE62 major transactivator and the cellular transcription factor Sp1. J. Biol. Chem., 278, 38068-38076, 2003.

Hay, J. and Ruyechan, W.T. Alphaherpesvirus DNA replication. In “Human herpesviruses: biology, therapy and immunoprophylaxis” Cambridge University Press. In press, 2004.

Baiker, A., Bagowski, C., Ito, H., Sommer, M., Zerboni, L., Fabel, K., Hay, J., Ruyechan, W.T and Arvin, A.M. The IE63 protein of VZV: 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.

Yang, M., Hay, J. and Ruyechan, W.T. The DNA element controlling expression of the VZV ORF 28 and 29 genes consists of two divergent unidirectional promoters which share a common USF site. J. Virol. 78, In press, 2004.

Cilloniz C. Jackson W. Grose C. Czechowski D. Hay J. Ruyechan WT. The varicella-zoster virus (VZV) ORF9 protein interacts with the IE62 major VZV transactivator. Journal of Virology. 81(2):761-74, 2007 Jan.


Abstracts are sent to two or three meetings each year, but are not listed here, since, normally, the subject of the abstract appears as a full paper.

Invited Presentations and Seminars:

On average, two or three of these invitations appears every year. I was in Egypt in 1996 and 1999, where I was invited to talk on VZV and hantaviruses. I was invited to organise a workshop in New Delhi, and to speak at two universities in Australia in March of 1997 and gave three talks in India again and Nepal in the summer of 2000. In 1997, I was in France, India and the UK, in addition to the usual national trips, and in 1998, 1999 and 2000 was back in France. In 1995 and 1999 I was invited to speak at meetings in Japan. In 2001 I was invited back to India to talk on alternative medicines and was in France in the late winter. This year, I will visit the VECTOR lab in Novosibirsk and will return to India for a series of seminars.