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We are interested in SV40 pathogenesis of human infections and disease, including the mechanism of a viral role in human cancer. SV40 is a small DNA virus, originally isolated from monkeys, 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.

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. We are studying the genetic and biological properties of SV40 variants isolated from human tumors and from other human infections, such as in transplant patients and those with kidney disease.

Our approach includes an analysis of SV40 effects on human lymphocytes and the development of a hamster model to dissect steps in SV40 tumorigenesis in vivo. The large tumor antigen (T-ag) of SV40 is the major transforming protein of the virus and is 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, as well as SV40 DNA from human tumors, has revealed the existence of a variable region at the C-terminus of T-ag. Studies are in progress to address the functional significance of the C-terminal domain of T-ag to the virus life cycle, cell transformation, and disease pathogenesis.

 

Recent Publications (PubMed)

Lednicky JA, Arrington AS, Stewart AR, Dai XM, Wong C, Jafar S, Murphey-Corb M and Butel JS. 1998. Natural isolates of simian virus 40 from immunocompromised monkeys display extensive genetic heterogeneity: new implications for polyomavirus disease. J Virol 72:3980-3990.

Butel JS and Lednicky JA. 1999. Cell and molecular biology of simian virus 40: implications for human infections and disease. J Natl Cancer Inst 91:119-134.

Butel JS, Jafar S, Wong C, Arrington AS, Opekun AR, Finegold MJ and Adam E. 1999. Evidence of SV40 infections in hospitalized children. Human Pathol 30:1496-1502.Butel JS. 2000. Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease. Carcinogenesis 21:405-426.

Gazdar AF, Butel JS and Carbone M. 2002. SV40 and human tumours: Myth, association or causality? Nature Rev Cancer 2:957-964.

Vilchez RA, Madden CR, Kozinetz CA, Halvorson SJ, White ZS, Jorgensen JL, Finch CJ and Butel JS. 2002. Association between simian virus 40 and non-Hodgkin lymphoma. Lancet 359:817-823.

Lednicky JA, Vilchez RA, Keitel WA, Visnegarwala F, White ZS, Kozinetz CA, Lewis DE and Butel JS. 2003. Polyomavirus JCV excretion and genotype analysis in HIV-infected patients receiving highly active antiretroviral therapy. AIDS 17:801-807.

Vilchez RA, Kozinetz CA, Arrington AS, Madden CR and Butel JS. 2003. Simian virus 40 in human cancers. Am J Med 114:675-684.