Simian virus 40 and its association with human lymphomas.

Abstract

Simian virus 40 (SV40) is a potent DNA tumor virus that is known to induce cancer in laboratory animals. The neoplasias induced by SV40 in animal models are brain cancers, mesothelioma, bone cancers, and systemic lymphomas. SV40 oncogenesis is mediated primarily by the viral large tumor antigen, which inactivates the tumor suppressor proteins p53 and pRb family members. Evidence indicates that SV40 is an emergent human pathogen and that a significant excess risk of SV40 is associated with primary human brain cancers, malignant mesothelioma, bone cancers, and non-Hodgkin's lymphoma. Therefore, the major types of tumors induced by SV40 in laboratory animals are the same as those human malignancies found to contain SV40 markers. Experimental and clinical data indicate that SV40 may be functionally important in the development of some of those malignancies. Recently, the Institute of Medicine of the National Academies concluded that SV40 infections could lead to cancer in humans under natural conditions (based on moderate strength biologic evidence). This review examines the data implicating SV40 in the pathogenesis of human lymphomas and discusses future directions to define the causative role for SV40 in these malignancies.