FUTURE DIRECTIONS AND CONCLUSIONS
Mounting evidence indicates that SV40 is a human pathogen, and current molecular biology, pathology, and clinical data, taken together, show that SV40 is significantly associated with and may be functionally important in the development of some human malignancies. Now, prospective studies are needed to determine the prevalence of SV40 infections in different human populations and to assess how the virus is transmitted from person to person. Indeed, the Institute of Medicine recognized that this gap in our understanding of the pathogenesis of SV40 in humans is important and recommended “targeted biological research” of SV40 in humans, including “further study of the transmissibility of SV40 in humans” (111). Considering that molecular biology approaches provide sensitive and specific approaches to analyze infectious diseases and malignancies with a possible infectious etiology, studies using these modern methods should be used to assess the distribution of SV40 infections and morbidity in humans today.
Although in vitro studies have established that SV40 disrupts critical cell cycle control pathways, it remains unknown whether these perturbations are sufficient for the virus to induce the development of malignancies in humans. Therefore, animal models that reproduce key features of SV40 infection and disease in humans are needed. Such models could provide precise evidence of the causal role of a particular pathway in SV40 pathogenesis in target tissues, allow further characterization of the molecular mechanisms of oncogenesis, and provide a preclinical system to test therapeutic interventions for these significant and increasingly common diseases.
ACKNOWLEDGMENTS
This work was supported in part by grant R21 CA96951 from the National Cancer Institute. Regis A. Vilchez is the recipient of the 2001 Junior Faculty Development Award from GlaxoSmithKline and the 2002 Translational Research Award from the Leukemia and Lymphoma Society.
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