Previous | Faculty Index | Next

The Butel laboratory is interested in polyomavirus pathogenesis of infections and disease, with a primary focus on polyomavirus SV40.  Originally isolated from monkeys, SV40 is a small DNA virus that is able to transform cells in culture and induce tumors in rodents. As a model tumor virus, SV40 has provided many fundamental insights into the molecular basis of carcinogenesis.

The large tumor antigen (T-ag) of SV40 is the major transforming protein of the virus, responsible for tumor causation in rodents and transformation of many cell types in culture. It is a complex protein that possesses multiple functions important for replicating the viral DNA and for dysregulating cell cycle control. Sequence analysis of viral isolates has revealed differences in the structure of the noncoding viral regulatory region as well as the existence of a variable region at the C-terminus of T-ag that can classify SV40 strains into genogroups.

We have developed the Syrian golden hamster small animal model to study SV40 pathogenesis of infection and disease.  Recent findings include the significant effect of the structure of the viral regulatory region on both oncogenic potential and vertical transmission in vivo.  There was no effect on transforming activity in vitro, indicating that strain-specific factors affect virus–host interactions that are not detectable using cultured cells.  The hamster model is being used to address the effect of SV40 genetic variations on patterns of viral infection that predispose to disease development.

Research in the last several years has established that authentic SV40 can cause human infections and is associated with certain types of human tumors, including brain tumors and lymphomas.  New findings related to human infections include the fecal excretion of polyomaviruses by humans, indicating a probable fecal–oral route of transmission; the detection of SV40 in normal and malignant lymphoid-rich tissues, suggesting that lymphoid cells are important in the pathogenesis of SV40 infections; and the variable frequency of SV40-positive lymphomas in two urban populations with different demographics, emphasizing that SV40 infection and disease likely reflect population differences.  Current research includes an analysis of SV40 effects on human lymphocytes and the role of SV40 microRNA in pathogenesis of infections.  Studies of the newly discovered human cancer virus, Merkel cell polyomavirus, are also in progress.

Recent Publications (PubMed)

Forsman, Z.H., Lednicky, J.A., Fox, G.E., Willson, R.C., White, Z.S., Halvorson, S.J., Wong, C., Lewis, A.M., Jr. and Butel, J.S.  Phylogenetic analysis of polyomavirus simian virus 40 from monkeys and humans reveals genetic variation.  J. Virol. 78:9306–9316, 2004.  PMCID: PMC506915.

Sroller, V., Vilchez, R.A., Stewart, A.R., Wong, C. and Butel, J.S.  Influence of the viral regulatory region on tumor induction by simian virus 40 in hamsters.  J. Virol. 82:871–879, 2008.  PMCID: PMC2224577.

Javier, R.T. and Butel, J.S.  The history of tumor virology.  Cancer Res. 68:7693–7706, 2008.  PMC Journal – In process.

McNees, A.L., Vilchez, R.A., Heard, T.C., Sroller, V., Wong, C., Herron, A.J., Hamilton, M.J., Davis, W.C. and Butel, J.S. SV40 lymphomagenesis in Syrian golden hamsters.  Virology384:114–124, 2009.  PMC Journal – In process.

Patel, N.C., Halvorson, S.J., Sroller, V., Arrington, A.S., Wong, C., Smith, E.O., Vilchez, R.A. and Butel, J.S.  Viral regulatory region effects on vertical transmission of polyomavirus SV40 in hamsters.  Virology 386:94–101, 2009.  PMC Journal – In process.

Vanchiere, J.A., Abudayyeh, S., Copeland, C.M., Lu, L.B., Graham, D.Y. and Butel, J.S.  Polyomavirus shedding in the stool of healthy adults.  J. Clin. Microbiol. 47:2388–2391, 2009.

Toracchio, S., Kozinetz, C.A., Killen, D.E., Sheehan, A.M., Banez, E.I., Ittmann, M.M., Sroller, V. and Butel, J.S.  Variable frequency of polyomavirus SV40 and herpesvirus EBV in lymphomas from two different urban population groups in Houston, Texas.  J. Clin. Virol. 46:154–160, 2009.