Simian Virus 40 and Human Disease

Abstract

Received 11 August 2004; accepted 11 August 2004; electronically published 16 November 2004. Reprints or correspondence: Dr. Keerti Shah, Dept. of Microbiology and Immunology, Johns Hopkins School of Public Health, 615 North Wolfe St., Baltimore, MD 21205 (kvshah @jhsph.edu). The Journal of Infectious Diseases 2004;190:2061–4 2004 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2004/19012-0001$15.00 The inadvertent and unrecognized presence of simian virus 40 (SV40) in the commercial inactivated Salk poliovaccines administered between 1955 and 1963 resulted in the potential exposure of millions of individuals, in the United States and elsewhere, to this polyomavirus of the rhesus macaque [1]. Many of the monkeykidney cultures used to prepare poliovirus pools were infected with the indigenous SV40. Soon after its discovery in 1960 [2], SV40 was found to be oncogenic in laboratory animals [3]. Therefore, the possibility that SV40 may cause human disease, particularly cancers, has been a topic of interest since the 1960s [4]. This debate has intensified during the past decade because several groups of investigators, using polymerase chain reaction (PCR) amplification methodology, have detected SV40 genomic sequences in a number of human cancers. These investigators have suggested that the virus contributes to the development of mesothelioma, osteosarcoma, pediatric and adult brain tumors, and non-Hodgkin lymphomas [5–8]. The reported presence of SV40 in tumors in individuals born after 1963 would seem to imply that SV40 is now established as a human infection circulating in communities via person-to-person contact [8]. Other investigators have been skeptical of these claims [9–12]; several groups have not been able to detect SV40 sequences in the aforementioned tumors [13–20], and epidemiologic studies have not revealed an increased risk of these cancers in populations exposed to SV40-contaminated poliovaccines or adenovirus vaccines [21– 23]. In addition to a large number of scientific publications, the controversy has spawned a report by the Institute of Medicine [24], a book in the popular press [25], and litigations. The evidence for the pathogenicity of SV40 in humans can be conveniently examined in 3 parts: (1) the nature of the human response after exposure to SV40, (2) the evidence that infection with SV40 has become established in humans, and (3) the evidence that infection with SV40 contributes to the development of human cancers.