Document Type

Theses, Masters

Rights

This item is available under a Creative Commons License for non-commercial use only

Disciplines

3. MEDICAL AND HEALTH SCIENCES

Publication Details

Successfully submitted for the award of Master of Philosophy (M.Phil.) to the Dublin Institute of Technology, 2010.

Abstract

The oncogenic DNA virus Simian virus 40 (SV40) was introduced into the human population as an inadvertent contaminant of polio vaccines that were prepared in cultures of primary monkey kidney cells. It is estimated that, as a result, millions of people worldwide were exposed to SV40 between the years 1955-1 963. Research indicates that the virus is still present in the human population today, based on the finding of neutralising antibodies and viral DNA sequences in children and adults. Of concern is that SV40 has also been detected in human tumours including primary brain cancer, malignant mesothelioma, bone tumours and systemic lymphomas. Recent studies have found a significant association of SV40 with certain types of Non-Hodgkin's Lymphoma (NHL). However, the interaction between SV40 and lymphocytes has not yet been fully characterised. In this study, the characteristics of SV40 infections were evaluated in human B and T lymphocyte cell lines. Three strains of SV40 were compared: wild type 776-1E with a single enhancer, 776-2E with a duplicated enhancer and a micro RNA mutant virus, 776-2E-SM. Following infection, cell proliferation and viability, cell surface marker expression, viral large tumour antigen (T-ag) expression, and quantification of viral genomes were measured. The results showed increased B cell proliferation and cell activation as shown by the upregulation of CD69. Downregulation of CD80, a co-stitnulatory molecule, was also observed. T-ag expression was detected in a small percentage of B cells and RQ-PCR analysis showed maintenance of the viral genome in B cells during passage of the cultures. In all, these initial observations indicate that some human B lymphocyte cell lines are susceptible to SV40 infection. Viral maintenance and oncoprotein expression in lymphocytes may bear relevance to SV40 persistence in the host and the detection of the virus in human lymphomas.

DOI

10.21427/D7161Z

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