Donald L. Holzschu, Ph.D.

     The goal of our research is to understand the mechanisms by which retroviruses replicate and cause disease.  These studies are timely because complex retroviruses cause diseases that are serious threats to general public health and it is likely that more retroviruses exist in nature that could possibly become human pathogens.  We are pursuing these investigations by focusing on the contribution of complex retrovirus accessory gene products to neoplasia in lower vertebrate model systems, i.e., fish.  Our work focuses on two diseases of walleye (Stizostedion vitreum), walleye dermal sarcoma (WDS) and walleye epidermal hyperplasia (WEH).  Interestingly, WDS and WEH are seasonal diseases, i.e. lesions are present on fish in the fall and winter, they become necrotic in the spring, and are absent in the summer.  WDS and WEH have been experimentally transmitted to walleye fingerlings using cell-free extracts from diseased tissues suggesting that an infectious agent induces disease.  We have molecularly cloned three retroviruses from WDS and WEH.  By characterizing viral gene expression patterns in lesions in the spring and fall, we intend to define the role of viral gene expression as it relates to tumor induction and, importantly, tumor regression.  Recently, we have discovered that these viruses encode cyclin D homologs that are expressed during the development of tumors and are highly expressed in regressing tumors.  Since overexpression of human cyclin D1 is observed in many tumors, we suggest that expression of the retroviral cyclins may play a central role in tumorigenesis.  This is the first discovery of oncogenic retroviruses that encode cyclins and it offers a unique opportunity to investigate the role of novel cyclins and retroviruses in tumorigenesis and tumor regression.

Selected References:

• Holzschu, D.L., G.A. Wooster and P.R. Bowser (1997) Experimental transmission of dermal sarcoma to saugers, Stizostedion canadense.  Dis. Aquat. Organisms.  Submitted for publication.

• Holzschu, D.L., M.A. Delaney, R.W. Renshaw and J.W. Casey (1997) The nucleotide sequence and spliced pol mRNA levels of the non-primate spumaretrovirus, bovine foamy virus.  J. Virol.  Submitted for publication.

• Quackenbush, S.L., D.L. Holzschu, P.R. Browser and J.W. Casey (1997) Transcriptional analysis of walleye dermal sarcoma virus (WDSV) Virology Accepted for publication.

• LaPierre, L.A., D.L. Holzschu, G.A. Wooster, P.R. Bowser and J.W. Casey (1997) Two closely related but distinct retroviruses are associated with walleye discrete epidermal hyperplasia.  J. Virol.  Submitted for publication.

• Bowser, P.R., G.A. Wooster, K. Earnest-Koons, L.A. LaPierre, D.L. Holzschu and J.W. Casey (1997) Experimental transmission of discrete epidermal hyperplasia in walleyes (Stizostedion vitreum).  Dis. Aquat. Anim. Health.  Submitted for publication.