Cell and molecular biology of simian virus 40: Implications for human infections and disease

Simian virus 40 (SV40), a polyomavirus of rhesus macaque origin, was discov ered in 1960 as a contaminant of polio vaccines that were distributed to mi llions of people from 1955 through early 1963, SV40 is a potent DNA tumor v irus that induces tumors in rodents and transforms many types of cells in c ulture, including those of human origin. This virus has been a favored labo ratory model for mechanistic studies of molecular processes in eukaryotic c ells and of cellular transformation. The viral replication protein, named l arge T antigen (T-ag), is also the viral oncoprotein, There is a single ser otype of SV40, but multiple strains of virus exist that are distinguishable by nucleotide differences in the regulatory region of the viral genome and in the part of the T-ag gene that encodes the protein's carboxyl terminus. Natural infections in monkeys by SV40 are usually benign but may become pa thogenic in immunocompromised animals, and multiple tissues can be infected . SV40 can replicate in certain types of simian and human cells. SV40-neutr alizing antibodies have been detected in individuals not exposed to contami nated polio vaccines. SV40 DNA has been identified in some normal human tis sues, and there are accumulating reports of detection of SV40 DNA and/or T- ag in a variety of human tumors. This review presents aspects of replicatio n and cell transformation by SV40 and considers their implications for huma n infections and disease pathogenesis by the virus. Critical assessment of virologic and epidemiologic data suggests a probable causative role for SV4 0 in certain human cancers, but additional studies are necessary to prove e tiology.