JC virus and simian virus 40 enhancers and transforming proteins: Role in determining tissue specificity and pathogenicity in transgenic mice

Lionel Feigenbaum, Steven Heye Hinrichs, Gilbert Jay

Research output: Contribution to journalComment/debate

51 Citations (Scopus)

Abstract

When introduced into the germ line of mice, the simian virus 40 (SV40) T antigen under the control of its own transcriptional enhancer and promoter selectively induced tumors in the choroid plexus as well as thymic hyperplasia and kidney pathology. In contrast, the JC virus (JCV) T antigen under the control of its own regulatory sequences induced hypomyelination of the central nervous system and tumors of neural origin. Since SV40 and JCV have extensive sequence homology, except for their transcriptional control regions, these observations suggest but do not prove that, although the diseases induced by the two viruses, are consequences of the transforming gene, they are determined predominantly by the respective viral enhancers and promoters. To test this hypothesis, the regulatory regions of the two viruses were exchanged, and transgenic mice were derived with either chimeric construct. Like wild-type JCV, the construct containing the SV40 T antigen under the control of the JCV regulatory region induced hypomyelination of the central nervous system and neural tumors. Surprisingly, mice with this construct also developed choroid plexus carcinomas. Like the wild-type SV40 transgenic mice, mice with the JCV T antigen under the control of the SV40 enhancer and promoter developed choroid plexus tumors and renal pathology. Unexpectedly, they also had hyperplasia of the thyroid follicular cells. These findings not only provide direct evidence for the specificity of the respective viral regulatory region but also, more importantly, show that the transforming genes play a critical role in determining viral pathogenesis.

Original languageEnglish (US)
Pages (from-to)1176-1182
Number of pages7
JournalJournal of virology
Volume66
Issue number2
StatePublished - Jan 1 1992

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JC polyomavirus
Simian virus 40
JC Virus
Organ Specificity
Transgenic Mice
Viral Tumor Antigens
Virulence
choroid plexus
pathogenicity
genetically modified organisms
Nucleic Acid Regulatory Sequences
Choroid Plexus Neoplasms
mice
antigens
Central Nervous System Neoplasms
neoplasms
promoter regions
Proteins
Oncogenes
hyperplasia

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

JC virus and simian virus 40 enhancers and transforming proteins : Role in determining tissue specificity and pathogenicity in transgenic mice. / Feigenbaum, Lionel; Hinrichs, Steven Heye; Jay, Gilbert.

In: Journal of virology, Vol. 66, No. 2, 01.01.1992, p. 1176-1182.

Research output: Contribution to journalComment/debate

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