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Journal of Virology, May 2003, p. 5039-5045, Vol. 77, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.9.5039-5045.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

MINIREVIEW

Simian Virus 40 Infection of Humans

Robert L. Garcea1 and Michael J. Imperiale2*

Section of Pediatric Oncology, University of Colorado School of Medicine, Denver, Colorado 80262,1 Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 481092


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INTRODUCTION
 
Since its discovery, simian virus 40 (SV40) has been one of the most intensely studied animal viruses. The molecular biology of SV40 has led to seminal discoveries in the fields of transcription, DNA replication, and oncogenic transformation (19). Over the last decade, provocative evidence has accumulated that suggests that SV40 may be a human pathogen. Does SV40 infect humans? If so, when did this monkey polyomavirus enter the human population and where is the reservoir? What is the behavior of SV40 in human cells? Does it cause or contribute to acute or chronic disease? Other comprehensive reviews have also addressed these issues, with a variety of emphases (8, 10, 52, 57, 107).

In 1960, Sweet and Hilleman first described an agent, which they named SV40, that induced cytopathic effects and vacuole formation in monkey cells (117). SV40 was isolated from normal monkey kidney cells, stocks of the Sabin poliovirus vaccine, and an adenovirus vaccine. The last two reagents were prepared in primary kidney cell cultures derived from rhesus monkeys. Subsequent analyses found that the Salk poliovirus vaccine administered from 1955 to 1963 in the United States was also contaminated with SV40, potentially exposing an estimated 100 million people (106). Although poliovirus in the Salk vaccine was inactivated by formalin treatment, the conditions were insufficient to completely inactivate SV40. Soon thereafter, it was demonstrated that SV40 could infect humans and also induce tumors in experimental animals (26, 28, 29, 42, 43). These observations raised concerns that vaccinated people worldwide may have been inadvertently exposed to an oncogenic virus. Early epidemiological studies allayed these fears, revealing no increased incidence of cancers directly related to immunization status (34, 35, 83, 106). However, these initial analyses were necessarily limited in that it was unknown whether (i) the virus could be transmitted, either horizontally or vertically; (ii) vaccinated, immunocompetent individuals would be at equal risk for development of cancer with others having defective immunity or a cancer predisposition; (iii) the power of the analysis was sufficient to detect increases in rare cancers; and (iv) SV40 normally circulated in humans before development of the poliovirus vaccine. A recent review of all epidemiological data by the Institute of Medicine concluded that evidence to date was "inadequate to accept or reject a causal relationship between SV40-containing poliovirus vaccines and cancer" (115). Criticisms included misclassification bias, lack of confidence intervals for the data, and "ecological" study design, which are unlikely to be remedied by further follow-up of the study populations.

A brief overview of the biology of SV40 is relevant to understand the concerns raised by these initial analyses (101). When SV40 infects its natural host, it initially undergoes a lytic replication cycle. The early viral genes encode the tumor (T) antigens: large T antigen (LT), small t antigen (ST), and 17K T antigen (also tiny T or T'). LT plays a dominant role in infection, repressing early viral gene transcription and stimulating late viral gene transcription (1, 54, 98, 121). LT is also an initiation factor for viral DNA replication (16, 97, 120, 123), recruiting the DNA polymerase {alpha}-primase complex to the origin of replication and acting as a helicase (21, 112, 114). Following the strategy of other DNA viruses, the SV40 early proteins dysregulate the cell cycle and impede cell apoptosis in order to maximize virus production. LT binds the members of the retinoblastoma protein family, pRb, p107, and p130, resulting in release and activation of E2F transcription factors, which stimulate expression of genes involved in S-phase progression and DNA synthesis (22, 27, 45). LT also binds p53 and inactivates its function, preventing the infected cell from undergoing apoptotic cell death (65, 71, 75). After viral DNA replication is under way, the infection enters the late phase, when viral structural proteins are synthesized and new virions are produced. Ultimately, the infected cell releases progeny virions, frequently but not always by cell lysis (18). The immune system is critical for controlling the initial lytic phase in vivo, quenching the initial infection to a state of persistent low-level or nonreplicating genomes (i.e., in the proximal renal tubular epithelium for SV40), with detectable lytic viral reactivation coincident only with host immunosuppression (48).

Some data on the infectivity of SV40 in humans were obtained from volunteers and individuals receiving contaminated vaccines. However, antibody data from many surveys must be viewed with the knowledge that the human BK virus (BKV) and JC virus (JCV) (closely related human polyomavirus family members) might give an indistinguishable response in these assays due to the high degree of cross-reactivity between capsid protein antigens. Melnick and Stinebaugh found SV40 (by cytopathic effects in monkey cells) in the stools of children 3 to 4 weeks after ingestion of 100 to 1,000 PFU of SV40 with oral poliovirus vaccine (77). Morris et al. gave SV40 intranasally to volunteers and found subclinical infections (82). They were able to isolate virus 7 to 11 days after administration from 3 of 8 subjects, and they detected antibody responses of various amplitudes. Horváth and Fornosi found SV40 excreted in the stools of 10 of 35 children 1 to 2 weeks after being given contaminated oral poliovirus vaccines (47). Thus, SV40 may replicate in humans after oral administration, but the efficiency and duration of the replication may be low in these immunocompetent subjects who were given small inocula.

The biology of SV40 in human cells was first studied in the 1960s with fibroblast cell lines or primary human fibroblast cell cultures (108). Whereas uninfected primary human fibroblasts can only be passaged a finite number of times before ceasing to divide and undergoing senescence, cell cultures infected with SV40 undergo a "crisis" at this same stage, followed by the outgrowth of a small number of cells that are phenotypically transformed (58). During the initial phase of the infection, generally the first 4 weeks, approximately 0.1% of the cells produce 500 to 1,000 virions per cell. Virus output from the culture then remains at a constant, very low level but with 100% of the cells producing virus at a rate of approximately 1 to 2 virions/cell (41, 42, 108). Once the cell culture progresses through crisis, virus production generally decreases, accompanied by a concomitant decrease in production of viral capsid proteins and an increase in the production of LT. One interpretation of these data is that the cells producing large amounts of virus are killed, but the cells that produce low levels of virus (as assayed by infectious center assays) survive. Finally, as the culture reaches its passage limit, most cells die, but those expressing a threshold level of LT overgrow the culture. Interestingly, the onset of transformation varies quite significantly in cells isolated from different individuals, ranging from 20 to almost 50 weeks in culture (91). Based on these early studies, human cells were termed semipermissive for SV40 growth (109). This nomenclature is confusing since the virus can clearly replicate in some human cell types more efficiently than in others, although the development of cytopathic effect is more rapid in African green monkey kidney cells.

More recent data have shown that while LT alone can immortalize human cells, ST is also necessary for eliciting a fully transformed phenotype (53, 93). For example, infection of cultured human mesothelial cells with SV40 establishes an apparently persistent infection in which little or no progeny virus is produced and the cells become transformed, a process requiring both LT and ST (4, 130). As described above, however, infected primary human fibroblasts can support robust lytic replication. The steady-state level of p53 in normal mesothelial cells is fourfold higher than that in fibroblasts, suggesting that the elevated p53 level interferes with the effect of LT upon DNA replication (4). Indeed, inhibition of p53 expression in mesothelial cells with an antisense oligonucleotide allows increased SV40 replication. Mesothelial cells therefore resemble infected late-passage primary fibroblasts with respect to virus production and growth characteristics.

SV40 is highly oncogenic in experimental animals and readily transforms rodent cells in culture (58). Hamsters inoculated with SV40 develop lymphomas, brain tumors, osteosarcomas, and mesotheliomas (25, 26, 28, 40, 56, 95). SV40 is likely oncogenic in rodents because LT is unable to interact functionally with the rodent DNA polymerase {alpha}-primase complex (84). In this setting, the oncogenic functions of the T antigens are engaged but the productive cycle is not completed, resulting in uncontrolled cell division rather than cell lysis. LT is both necessary and sufficient for initiation and maintenance of transformation of rodent cells in tissue culture in most instances (7). Under certain conditions, however, usually involving primary cells in the absence of growth factors, ST is also required. ST functions by inhibiting the activity of the cellular phosphatase PP2A, resulting in activation of cell growth signal transduction pathways (90, 100). Mice that are transgenic for LT transcriptionally regulated by tissue-specific promoters develop tumors in those tissues (for an example, see reference 105). Transgenic mice in which LT expression is regulated by the native viral promoter elements specifically develop tumors of the choroid plexus (6), the specialized epithelial structure of the brain ependymal lining that produces cerebrospinal fluid. This finding is interesting in view of the discovery of SV40 DNA in certain brain tumors, as discussed below.

After the discovery of SV40's tumorigenic and cell transformation properties, a wave of studies in the 1960s and 1970s pursued the identification of viral oncogenic agents in humans (9). SV40 DNA was detected on rare occasions, usually in brain tumors, using relatively low-sensitivity Southern hybridization techniques, immunostaining for LT, and electron microscopy (2, 61, 62, 76, 104, 118). Also during this period, the distinctly human polyomaviruses BKV and JCV were identified, and the destructive brain white matter disease progressive multifocal leukoencephalopathy was attributed to JCV infection (39, 86, 88). These human viruses were also shown to induce tumors in animals and to transform rodent and human cells in culture (20, 33, 94, 113, 127, 132). However, virtually all investigations failed to reveal any significant associations between human malignancy and these suspected oncogenic viruses. With the discovery of oncogenes, the emphasis in cancer research shifted from viruses to genomic mutations.

In 1992, Bergsagel et al. reported finding SV40-like DNA sequences in two types of rare childhood brain tumors, choroid plexus neoplasms and ependymomas, by use of PCR detection (3). This study was prompted by previous transgenic mouse studies and sought to determine whether the human polyomaviruses BKV and JCV might be present in these tumors. The PCR primers were designed to amplify the pRb binding domain of LT, which is highly conserved among all polyomavirus LT proteins. Unexpectedly, DNA sequences consistent with SV40 rather than BKV or JCV LT were amplified. Immunohistochemical nuclear staining for LT was also positive in a fraction of tumors. Subsequently, DNAs isolated from these same tumor types were evaluated by Lednicky et al., who verified the previous amplification results (67). In addition, they (i) found an unduplicated enhancer element, i.e., a single 72-bp repeat, characteristic of direct primate SV40 isolates but not laboratory virus strains (50), (ii) detected sequence variability in the carboxy terminus of different LT genes, and (iii) rescued infectious SV40 from one choroid plexus tumor whose DNA was directly isolated from fresh tumor tissue instead of from paraffin-embedded sections. Observations of SV40-like sequences in brain tumors continue to be reported (49, 59, 74).

With the same primers used by Bergsagel, Carbone et al. then detected SV40 sequences in human mesotheliomas (12). A mesothelioma is an aggressive tumor of the lung pleura, pericardium, or peritoneum and has been linked to asbestos exposure. Carbone et al. had previously found that SV40 could induce mesotheliomas when injected into the pleural cavities of experimental animals (17). In extracts prepared from human mesotheliomas, p53, pRb, p107, and p130 can be coimmunoprecipitated with LT (13, 23). Microdissection studies have shown that SV40 DNA is present in tumor tissue but not in the normal surrounding lung (111). Adenovirus vectors expressing antisense SV40 LT arrest the growth of SV40-positive mesothelioma tumor cells and cause them to undergo apoptosis (126). As is the case for brain tumors, however, LT expression is not detectable by immunohistochemistry in all mesothelioma tumor cells, and the calculated amount of SV40 DNA may be less than one copy per cell. The number of reports identifying SV40 DNA in mesotheliomas far outnumber that for any other tumor type.

Other human tumors frequently associated with SV40-like DNA sequences are osteosarcomas and related bone tumors (14, 37, 68, 78, 129). When PCR strategies similar to those described above are used, approximately 30 to 40% of analyzed bone tumors are positive for viral DNA. SV40 sequences have been detected by Southern blot analysis in osteosarcoma tumor DNA, but this finding is rare. Most recently, in studies using the same primers, adult large-cell non-Hodgkin's lymphomas (NHL) were reported to contain SV40-like sequences (110, 125). Interestingly, the incidence of NHL has risen dramatically in the past three decades, similar to the increased incidence of mesotheliomas. In addition, throughout the past 10 years a potpourri of other tumors and tissues have been reported positive for SV40 DNA, although occasionally the results have not been independently confirmed by other groups (73, 74, 85). The search has extended to an association of SV40 with human renal disease, JCV with medulloblastomas and colon cancer, and BKV with neuroblastomas and urinary tract tumors (24, 32, 63, 64, 70, 81). The literature citations have proliferated, suggesting that SV40 has become epidemic or at least has developed into a cottage industry for PCR detection.

So why is there skepticism and controversy about the role of SV40 in human cancer? The following confounding technical issues remain problematic: (i) detection of SV40 DNA requires a large number of PCR cycles, i.e., 40 to 60, raising the question of how many cells contain viral DNA and how many genomes there are per cell; (ii) the method of DNA isolation has been questioned (e.g., some commercial extraction kits may lose small quantities of episomal viral DNA) (66); (iii) amplification of smaller genomic segments seems more prone to yield nonspecific products than amplification of larger fragments and these are often judged positive (e.g., the 572-bp fragment spanning the LT intron versus the 105-bp pRb binding region); (iv) DNA sequence verification of amplified products has not always been complete; (v) reproducibility among laboratories studying similar tumor types has not been universal (31, 55, 60, 99, 116, 128); (vi) lab contamination may confound some results (e.g., cloning vectors containing SV40 sequences have been suggested as sources of contamination, although those sequences should not be amplified by commonly used primers); (vii) the same PCR primer pairs have been used in most studies without attempts to improve upon their design or optimize their use; and (viii) the antibodies used for LT detection are not specific for SV40 but also cross-react with LT from JCV and BKV. Although detection of SV40 DNA by PCR for particular cancers (e.g., mesotheliomas and NHL) may reach 30 to 40% of cases, the lack of detectable SV40 DNA or LT in every cell of these tumors distinguishes the association from the recognized etiologic connection of high-risk human papillomaviruses with cervical cancer or Epstein-Barr virus with lymphoproliferative lesions in immunocompromised individuals (89, 131). This lack of uniform presence of the viral DNA, coupled with concerns about PCR techniques, a past history of negative associations, the litigious cloud of contaminated poliovirus vaccines, a paucity of information on the SV40 life cycle in relevant human cell types, and a scientific culture now emphasizing oncogenes rather than oncoviruses, have made the existence of SV40 in humans, let alone its causality in disease, a "hard sell."

Gradually, however, the case for SV40 infecting humans and contributing to cancer has become more compelling, supported by both experimental and circumstantial evidence: (i) microdissection identified amplifiable SV40 DNA in mesotheliomas but not in adjacent normal tissues (111), (ii) SV40 DNA has been detected in an osteosarcoma by Southern hybridization (78), (iii) Li-Fraumeni syndrome patients appear to have a unique susceptibility to polyomaviruses (see below) (72), (iv) a single 72-bp repeat identified in the viral enhancer of SV40 DNA isolated from choroid plexus tumors is characteristic of virus isolates from monkeys (50, 67), and (v) infectious SV40 was isolated from choroid plexus tumor tissue (67). In an attempt to address the variance in detection, two multilaboratory studies were undertaken to examine the presence of SV40 in mesothelioma samples (51, 122). Unfortunately, both studies had technical flaws and their conclusions were contradictory, leaving the question of why there are differences in detection unsettled. However, analysis of samples from geographically distinct populations has provided unique naturally occurring controls. Mesothelioma samples from Finland, where contaminated poliovirus vaccines were not administered, are negative for SV40 DNA (46). A recent study of a Turkish community with a very high frequency of mesothelioma linked to environmental asbestos exposure also found no evidence for SV40 DNA in the tumors from this unvaccinated population (30). Thus, SV40 DNA is only found in mesotheliomas in areas of the world where the contaminated vaccines were used, indirectly suggesting a link between SV40 and the cancer.

If present, how might SV40 be selectively oncogenic in some tissues and/or individuals? Factors may include the sensitivity of the particular tissue to pRb and p53 dysfunction, activity of the viral promoter, tropism or targeting of the virus to specific cell types, genetic predisposition, and immune status. As demonstrated with transgenic mice, choroid plexus cells are unusually sensitive to p53 and pRb mutations, leading to rapid malignant transformation (15, 124). The choroid plexus may be functionally related to proximal renal tubular epithelium (i.e., an ion pumping machine), and thus factors in these cells may be similarly permissive for viral gene expression. In pRb-deficient patients, osteosarcomas are the second most common neoplasm after retinoblastoma. Thus, osteoblasts may be very susceptible to pRb deficiencies (69). Li-Fraumeni syndrome patients, who are heterozygous for germ line p53 mutations, seem unusually susceptible to SV40 infection, possibly because inactivation of the remaining wild-type p53 allele can be accomplished with lower T-antigen expression levels. It may also be possible that SV40 can establish an initial infection in these individuals more easily if there is less p53 present to interfere with viral replication. Li-Fraumeni syndrome patients have been described who develop choroid plexus tumors and osteosarcomas that contain SV40 DNA, but other tumor types within the same individual, such as muscle rhabdomyosarcomas, are not associated with SV40 DNA sequences (72). This tissue preference may occur because of cell type variations in viral promoter activity, virus receptors, or the relative importance of p53 and pRb for the initial oncogenic event.

More difficult to explain is the apparent lack of SV40 DNA (calculated) or protein (detected by immunohistochemistry) in all the cells of a tumor. Possible reasons include the following: (i) levels of LT protein expression below the limits of detection; (ii) a paracrine mechanism by which LT-expressing cells secrete a growth factor, e.g., insulin-like growth factor type I (IGF-I), affecting surrounding cells that do not contain SV40 (92); (iii) isolation of the tumor after most virus-containing cells have died (hit-and-run), leaving only tumor cells with additional mutations contributing to proliferation (i.e., LT and/or ST causes chromosomal instability [36, 96] and is then lost in the transformed cells); and (iv) SV40 not contributing to tumorigenesis but being present because the tumor growth state is permissive for virus replication or LT protein expression.

Cause and effect have been indirectly addressed by antisense LT expression in cultured cells, which implies that, at least in mesothelial cells, LT makes a significant contribution to the ability of these cells to grow in culture (126). One approach to explore a causal role of LT in malignancy might be to correlate the p53 and RB1 status of tumors with the presence of SV40 sequences. Inactivation of these pathways by mutation would not be necessary if LT was continuously produced and active. For example, the frequency of p53 and RB1 gene mutations is low in mesothelioma and thus LT may be functionally important (11). Osteosarcomas with wild-type p53 and those with defective p53 would be candidates for such a comparative analysis.

What is needed to enhance our understanding of SV40 infection in humans and the role of SV40 in human malignancies? Current data on SV40 replication and transmission in human populations are nearly uninterpretable and will not improve until a highly specific serological assay for SV40 is used to analyze clinical samples. Such an immunoassay has been difficult to devise because of extensive cross-reactivity of the SV40 capsid proteins with those of BKV and JCV. Virus neutralization assays are extremely labor-intensive and have not been directly compared among the viruses. Recently, however, recombinant VP1 capsid proteins for SV40, JCV, and BKV have been prepared as virus-like particle preparations for use in enzyme-linked immunosorbent assays (K. Shah and D. Galloway, personal communications). The initial serological studies using these reagents have not detected specific or robust SV40 immune responses in any samples tested. A small fraction (5 to 7%) of sera (K. Shah, personal communication) have low-level reactivity with SV40 VP1 that may be due to cross-reactivity with JCV or BKV VP1 or to a transient SV40 infection. These assays will now permit case-controlled studies, however, comparing individuals with SV40-associated malignancies to control populations.

Seroepidemiologic studies would permit an assessment of SV40 prevalence in the population, suggest its mode of transmission, and correlate seropositivity with disease or perhaps even predisposition to disease. From current PCR data it appears that individuals who were never exposed to contaminated vaccines have been infected with SV40, suggesting that the virus has established itself as a human pathogen. The mode of transmission may be extrapolated from that of BKV and JCV. Studies have shown that these two viruses infect virtually 100% of most human populations, BKV during early childhood and JCV peaking in early adolescence (38, 87, 119). While both viruses ultimately establish a persistent infection in the urinary tract and perhaps in the central nervous system, recent reports have found the presence of viral DNA in tonsillar tissue (44, 79, 80). The presence of virus in the upper respiratory tract, along with the young age of seroconversion, suggests that SV40 may spread through a respiratory or fomite, i.e., hand-to-mouth, route. From this initial portal of entry, the virus must have access to the circulatory and/or lymphatic system in order to reach its presumed site of persistence, the kidney, or the tissues and organs that give rise to the tumors associated with the virus. By analogy with other viruses, such systemic virus spread, or virus replication at sites of tumor induction, should elicit a detectable immune response.

More information is needed concerning the SV40 life cycle in human cells. Are there differences in permissiveness among human cell types? Is there a correlation of oncogenicity with levels of p53 in different cell types, e.g., as seen in mesothelial cells? Are there differences among cell types in viral genome persistence? Are secondary cellular mutations induced when LT is highly expressed, and do the mutations lead to stable populations of dominantly replicating clones that now lack viral DNA? Finally, the role of the immune system in all phases of the disease process is undoubtedly profoundly important. Unlike most putative tumor antigens, SV40 T antigens are not self antigens and therefore ought to be recognized by the immune system. Does the tumor provide an immunoprivileged site in which these antigens are not detected? In rodent SV40 tumor models, the immune response against LT is robust and usually results in clearance of the virus, making this possibility unlikely (102, 103). Moreover, humans can apparently mount a cytotoxic lymphocyte immune response to LT (5). However, there must be some coexistence of the immune system and the virus to achieve persistence. Thus, defects in the immune system might permit virus persistence to develop into an oncogenic state. In this regard, it would be useful to study SV40 infections in immunocompromised individuals. Based on the evolving SV40 story, it also seems prudent to look more carefully at a possible role of BKV and JCV in human neoplasms, as there is no doubt that these viruses are endemic in most human populations.

At this time, some members of the jury remain undecided about a role for SV40 in human disease. Seroepidemiology and a basic understanding of virus biology in humans are essential pieces missing from the puzzle. Perhaps we expect SV40 to follow the "rules" for other oncogenic viruses such as human papillomavirus and Epstein-Barr virus. Rather, SV40 may be generating novel rules, leading the way as it has before into new paradigms of virus biology and pathogenesis.


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ACKNOWLEDGMENTS
 
We thank David Malkin, Kay Holmes, Janet Butel, Rosemary Rochford, and Jon Low for their helpful suggestions and comments.


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FOOTNOTES
 
* Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Michigan Medical School, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0942. Phone: (734) 763-9162. Fax: (734) 615-6560. E-mail: imperial{at}umich.edu. Back


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REFERENCES
 
    1
  1. Alwine, J. C., S. I. Reed, and G. R. Stark. 1977. Characterization of the autoregulation of simian virus 40 gene A. J. Virol. 24:22-27.[Abstract/Free Full Text]
    2. 2
  2. Bastian, G. O. 1971. Papova-like virus particles in a human brain tumor. Lab. Investig. 25:169-175.[Medline]
    3. 3
  3. Bergsagel, D. J., M. J. Finegold, J. S. Butel, W. J. Kupsky, and R. L. Garcea. 1992. DNA sequences similar to those of simian virus 40 in ependymomas and choroid plexus tumors of childhood. N. Engl. J. Med. 326:988-993.[Abstract]
    4. 4
  4. Bocchetta, M., I. Di Resta, A. Powers, R. Fresco, A. Tosolini, J. R. Testa, H. I. Pass, P. Rizzo, and M. Carbone. 2000. Human mesothelial cells are unusually susceptible to simian virus 40-mediated transformation and asbestos cocarcinogenicity. Proc. Natl. Acad. Sci. USA 97:10214-10219.[Abstract/Free Full Text]
    5. 5
  5. Bright, R. K., E. T. Kimchi, M. H. Shearer, R. C. Kennedy, and H. I. Pass. 2002. SV40 Tag-specific cytotoxic T lymphocytes generated from the peripheral blood of malignant pleural mesothelioma patients. Cancer Immunol. Immunother. 50:682-690.[CrossRef][Medline]
    6. 6
  6. Brinster, R. L., H. Y. Chen, A. Messing, T. van Dyke, A. J. Levine, and R. D. Palmiter. 1984. Transgenic mice harboring SV40 T-antigen genes develop characteristic brain tumors. Cell 37:367-379.[CrossRef][Medline]
    7. 7
  7. Brockman, W. W. 1978. Transformation of BALB/c-3T3 cells by tsA mutants of simian virus 40: temperature sensitivity of the transformed phenotype and retransformation by wild-type virus. J. Virol. 25:860-870.[Abstract/Free Full Text]
    8. 8
  8. Brown, F., and A. M. J. Lewis (ed.). 1997. Simian virus 40 (SV40): a possible human polyomavirus. Developments in biological standarization, vol. 94. Karger, Basel, Switzerland.
    9. 9
  9. Butel, J. S. 2000. Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease. Carcinogenesis 21:405-426.[Abstract/Free Full Text]
    10. 10
  10. Butel, J. S., and J. A. Lednicky. 1999. Cell and molecular biology of simian virus 40: implications for human infections and disease. J. Natl. Cancer Inst. 91:119-134.
    11. 11
  11. Carbone, M., R. A. Kratzke, and J. R. Testa. 2002. The pathogenesis of mesothelioma. Semin. Oncol. 29:2-17.
    12. 12
  12. Carbone, M., H. I. Pass, P. Rizzo, M. Marinetti, M. DiMuzio, D. J. Y. Mew, A. S. Levine, and A. Procopio. 1994. Simian virus 40-like DNA sequences in human pleural mesothelioma. Oncogene 9:1781-1790.[Medline]
    13. 13
  13. Carbone, M., P. Rizzo, P. M. Grimley, A. Procopio, D. J. Á. Mew, V. Shridhar, A. de Bartolomeis, V. Esposito, M. T. Giuliano, S. M. Steinberg, A. S. Levine, A. Giordano, and H. I. Pass. 1997. Simian virus-40 large-T antigen binds p53 in human mesotheliomas. Nat. Med. 3:908-912.[CrossRef][Medline]
    14. 14
  14. Carbone, M., P. Rizzo, A. Procopio, M. Giuliano, H. I. Pass, M. C. Gebhardt, C. Mangham, M. Hansen, D. G. Malkin, G. Bushart, F. Pompetti, P. Picci, A. S. Levine, D. J. Bersagel, and R. L. Garcea. 1996. SV40-like sequences in human bone tumors. Oncogene 13:527-535.[Medline]
    15. 15
  15. Chen, J., G. J. Tobin, J. M. Pipas, and T. Van Dyke. 1992. T-antigen mutant activities in vivo: roles of p53 and pRB binding in tumorigenesis of the choroid plexus. Oncogene 7:1167-1175.[Medline]
    16. 16
  16. Chou, J. Y., J. Avila, and R. G. Martin. 1974. Viral DNA synthesis in cells infected by temperature-sensitive mutants of simian virus 40. J. Virol. 14:116-124.[Abstract/Free Full Text]
    17. 17
  17. Cicala, C., F. Pompetti, and M. Carbone. 1993. SV40 induces mesotheliomas in hamsters. Am. J. Pathol. 142:1524-1533.[Abstract]
    18. 18
  18. Clayson, E. T., L. V. Brando, and R. W. Compans. 1989. Release of simian virus 40 virions from epithelial cells is polarized and occurs without cell lysis. J. Virol. 63:2278-2288.[Abstract/Free Full Text]
    19. 19
  19. Cole, C. N., and S. D. Conzen. 2001. Polyomaviridae: the viruses and their replication, p. 2141-2174. In D. M. Knipe and P. M. Howley (ed.), Fields virology. Lippincott-Raven Publishers, Philadelphia, Pa.
    20. 20
  20. Dalrymple, S. A., and K. L. Beemon. 1990. BK virus T antigens induce kidney carcinomas and thymoproliferative disorders in transgenic mice. J. Virol. 64:1182-1191.[Abstract/Free Full Text]
    21. 21
  21. Dean, F. B., P. Bullock, Y. Murakami, C. R. Wobbe, L. Weissbach, and J. Hurwitz. 1987. Simian virus 40 (SV40) DNA replication: SV40 large T antigen unwinds DNA containing the SV40 origin of replication. Proc. Natl. Acad. Sci. USA 84:16-20.[Abstract/Free Full Text]
    22. 22
  22. DeCaprio, J. A., J. W. Ludlow, J. Figge, J.-Y. Shew, C.-M. Huang, W.-H. Lee, E. Marsilio, E. Paucha, and D. M. Livingston. 1988. SV40 large tumor antigen forms a specific complex with the product of the retinoblastoma susceptibility gene. Cell 54:275-283.[CrossRef][Medline]
    23. 23
  23. De Luca, A., A. Baldi, V. Esposito, C. M. Howard, L. Bagella, P. Rizzo, M. Caputi, H. I. Pass, G. G. Giordano, F. Baldi, M. Carbone, and A. Giordano. 1997. The retinoblastoma gene family pRb/p105, p107, pRb2/p130 and simian virus-40 large T-antigen in human mesotheliomas. Nat. Med. 3:913-916.[CrossRef][Medline]
    24. 24
  24. Del Valle, L., J. Gordon, S. Enam, S. Delbue, S. Croul, S. Abraham, S. Radhakrishnan, M. Assimakopoulou, C. D. Katsetos, and K. Khalili. 2002. Expression of human neurotropic polyomavirus JCV late gene product agnoprotein in human medulloblastoma. J. Natl. Cancer Inst. 94:267-273.[Abstract/Free Full Text]
    25. 25
  25. Diamandopoulos, G. T. 1973. Induction of lymphocytic leukemia, lymphosarcoma, reticulum cell sarcoma, and osteogenic sarcoma in the Syrian golden hamster by oncogenic DNA simian virus 40. J. Natl. Cancer Inst. 50:1347-1365.
    26. 26
  26. Diamandopoulos, G. T. 1972. Leukemia, lymphoma, and osteosarcoma induced in the Syrian golden hamster by simian virus 40. Science 176:173-175.[Abstract/Free Full Text]
    27. 27
  27. Dyson, N., R. Bernards, S. H. Friend, L. R. Gooding, J. A. Hassell, E. O. Major, J. M. Pipas, T. Van Dyke, and E. Harlow. 1990. Large T antigens of many polyomaviruses are able to form complexes with the retinoblastoma protein. J. Virol. 64:1353-1356.[Abstract/Free Full Text]
    28. 28
  28. Eddy, B. E. 1962. Tumors produced in hamsters by SV40. Fed. Proc. 21:930-935.
    29. 29
  29. Eddy, B. E., G. S. Borman, W. H. Berkeley, and R. D. Young. 1961. Tumors induced in hamsters by injection of rhesus monkey kidney cell extracts. Proc. Soc. Exp. Biol. Med. 107:191-197.
    30. 30
  30. Emri, S., T. Kocagoz, A. Olut, Y. Gungen, L. Mutti, and Y. I. Baris. 2000. Simian virus 40 is not a cofactor in the pathogenesis of environmentally induced malignant pleural mesothelioma in Turkey. Anti-Cancer Res. 20:891-894.[Medline]
    31. 31
  31. Engels, E. A., C. Sarkar, R. W. Daniel, P. E. Gravitt, K. Verma, M. Quezado, and K. V. Shah. 2002. Absence of simian virus 40 in human brain tumors from northern India. Int. J. Cancer 101:348-352.[CrossRef][Medline]
    32. 32
  32. Flægstad, T., P. A. Andresen, J. I. Johnsen, S. K. Asomani, G.-E. Jørgensen, S. Vignarajan, A. Kjuul, P. Kogner, and T. Traavik. 1999. A possible contributory role of BK virus infection in neuroblastoma development. Cancer Res. 59:1160-1163.[Abstract/Free Full Text]
    33. 33
  33. Franks, R. R., A. Rencic, J. Gordon, P. W. Zoltick, M. Curtis, R. L. Knobler, and K. Khalili. 1996. Formation of undifferentiated mesenteric tumors in transgenic mice expressing human neurotropic polyomavirus early protein. Oncogene 12:2573-2578.[Medline]
    34. 34
  34. Fraumeni, J. F. J., F. Ederer, and R. W. Miller. 1963. An evaluation of the carcinogenicity of simian virus 40 in man. JAMA 185:713-718.
    35. 35
  35. Fraumeni, J. F. J., C. R. Stark, E. Gold, and M. L. Lepow. 1970. Simian virus 40 in polio vaccine: follow-up of newborn recipients. Science 167:59-60.[Abstract/Free Full Text]
    36. 36
  36. Gaillard, S., K. M. Fahrbach, R. Parkati, and K. Rundell. 2001. Overexpression of simian virus 40 small-t antigen blocks centrosome function and mitotic progression in human fibroblasts. J. Virol. 75:9799-9807.[Abstract/Free Full Text]
    37. 37
  37. Gamberi, G., M. S. Benassi, F. Pompetti, C. Ferrari, P. Ragazzini, M. R. Sollazzo, L. Molendini, M. Meril, G. Magagnoli, F. Chiesa, A. G. Gobbi, A. Powers, and P. Picci. 2000. Presence and expression of the simian virus-40 genome in human giant cell tumors of bone. Genes Chromosomes Cancer 28:23-30.[CrossRef][Medline]
    38. 38
  38. Gardner, S. D. 1973. Prevalence in England of antibody to human polyomavirus (B.K.). Br. Med. J. 1:77-78.
    39. 39
  39. Gardner, S. D., A. M. Field, D. V. Coleman, and B. Hume. 1971. New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet i:1253-1257.
    40. 40
  40. Gerber, P., and R. L. Kirschstein. 1962. SV40-induced ependymomas in newborn hamsters. Virology 18:582-588.[CrossRef][Medline]
    41. 41
  41. Girardi, A. J., F. C. Jensen, and H. Koprowski. 1965. SV40-induced transformation of human diploid cells: crisis and recovery. J. Cell. Comp. Physiol. 65:69-84.
    42. 42
  42. Girardi, A. J., B. H. Sweet, and M. R. Hilleman. 1963. Factors influencing tumor induction in hamsters by vacuolating virus, SV40. Proc. Soc. Exp. Biol. Med. 112:662-667.
    43. 43
  43. Girardi, A. J., B. H. Sweet, V. B. Slotnick, and M. R. Hilleman. 1962. Development of tumors in hamsters inoculated in the neo-natal period with vacuolating virus, SV40. Proc. Soc. Exp. Biol. Med. 109:649-660.
    44. 44
  44. Goudsmit, J., P. Wertheim-van Dillen, A. vanStrien, and J. van der Noordaa. 1982. The role of BK virus in acute respiratory tract disease and the presence of BKV DNA in tonsils. J. Med. Virol. 10:91-99.[Medline]
    45. 45
  45. Hannon, G. J., D. Demetrick, and D. Beach. 1993. Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins. Genes Dev. 7:2378-2391.[Abstract/Free Full Text]
    46. 46
  46. Hirvonen, A., K. Mattson, A. Karjalainen, T. Ollikainen, L. Tammilehto, T. Hovi, H. Vainio, H. I. Pass, I. Di Resta, M. Carbone, and K. Linnainmaa. 1999. SV40-like DNA sequences not detectable in Finnish mesothelioma patients not exposed to SV40 contaminated poliovaccines. Mol. Carcinog. 26:93-99.[CrossRef][Medline]
    47. 47
  47. Horváth, B. L., and F. Fornosi. 1964. Excretion of SV40 virus after oral administration of contaminated polio vaccine. Acta Microbiol. Acad. Sci. Hung. 11:271-275.[Medline]
    48. 48
  48. Horvath, C. J., M. A. Simon, D. J. Bergsagel, D. R. Pauley, N. W. King, R. L. Garcea, and D. J. Ringler. 1992. Simian virus 40 (SV40)-induced disease in rhesus monkeys with simian acquired immunodeficiency syndrome. Am. J. Pathol. 140:1431-1440.[Abstract]
    49. 49
  49. Huang, H., R. Reis, Y. Yonekawa, J. M. Lopes, P. Kleihues, and H. Ohgaki. 1999. Identification in human brain tumors of DNA sequences specific for SV40 large T antigen. Brain Pathol. 9:33-44.[Medline]
    50. 50
  50. Ilyinskii, P. O., M. D. Daniel, C. J. Horvath, and R. C. Desrosiers. 1992. Genetic analysis of simian virus 40 from brains and kidneys of macaque monkeys. J. Virol. 66:6353-6360.[Abstract/Free Full Text]
    51. 51
  51. International SV40 Working Group. 2001. A multicenter evaluation of assays for detection of SV40 DNA and results in masked mesothelioma specimens. Cancer Epidemiol. Biomark. Prev. 10:523-532.[Abstract/Free Full Text]
    52. 52
  52. Jasani, B., A. Cristaudo, S. A. Emri, A. F. Gazdar, A. Gibbs, B. Krynska, C. Miller, L. Mutti, C. Radu, M. Tognon, and A. Procopio. 2001. Association of SV40 with human tumors. Semin. Cancer Biol. 11:49-61.[CrossRef][Medline]
    53. 53
  53. Jha, K. K., S. Banga, V. Palejawala, and H. L. Ozer. 1998. SV40-mediated immortalization. Exp. Cell Res. 245:1-7.[CrossRef][Medline]
    54. 54
  54. Khoury, G., and E. May. 1977. Regulation of early and late simian virus 40 transcription: overproduction of early viral RNA in the absence of a functional T-antigen. J. Virol. 23:167-176.[Abstract/Free Full Text]
    55. 55
  55. Kim, J. Y., I. J. Koralnik, M. LeFave, R. A. Segal, L. A. Pfister, and S. L. Pomeroy. 2002. Medulloblastomas and primitive neuroectodermal tumors rarely contain polyomavirus DNA sequences. Neuro-Oncol. 4:165-170.[Abstract]
    56. 56
  56. Kirschstein, R. L., and P. Gerber. 1962. Ependymomas produced after intracerebral inoculation of SV40 into new-born hamsters. Nature 195:299-300.[Medline]
    57. 57
  57. Klein, G., A. Powers, and C. Croce. 2002. Association of SV40 with human tumors. Oncogene 21:1141-1149.[CrossRef][Medline]
    58. 58
  58. Koprowski, H., J. A. Ponten, F. Jensen, R. G. Ravdin, P. Moorhead, and E. Saksela. 1962. Transformation of cultures of human tissue infected with simian virus 40. J. Cell. Comp. Physiol. 59:281-292.[CrossRef]
    59. 59
  59. Kouhata, T., K. Fukuyama, N. Hagihara, and K. Tabuchi. 2001. Detection of simian virus 40 DNA sequence in human primary glioblastomas multiforme. J. Neurosurg. 95:96-101.
    60. 60
  60. Krainer, M., T. Schenk, C. C. Zielinski, and C. Muller. 1995. Failure to confirm presence of SV40 sequences in human tumors. Eur. J. Cancer 31:1893.[CrossRef]
    61. 61
  61. Krieg, P., E. Antmann, D. Jonas, H. Fischer, K. Zang, and G. Sauer. 1981. Episomal simian virus 40 genomes in human brain tumors. Proc. Natl. Acad. Sci. USA 78:6446-6450.[Abstract/Free Full Text]
    62. 62
  62. Krieg, P., and G. Scherer. 1984. Cloning of SV40 genomes from human brain tumors. Virology 138:336-340.[CrossRef][Medline]
    63. 63
  63. Krynska, B., L. D. Valle, S. Croul, J. Gordon, C. D. Katsetos, M. Carbone, A. Giordano, and K. Khalili. 1999. Detection of human neurotropic JC virus DNA sequence and expression of the viral oncogenic protein in pediatric medulloblastomas. Proc. Natl. Acad. Sci. USA 96:11519-11524.[Abstract/Free Full Text]
    64. 64
  64. Laghi, L., A. E. Randolph, D. P. Chauhan, G. Marra, E. O. Major, J. V. Neel, and C. R. Boland. 1999. JC virus DNA is present in the mucosa of the human colon and in colorectal cancers. Proc. Natl. Acad. Sci. USA 96:7484-7489.[Abstract/Free Full Text]
    65. 65
  65. Lane, D. P., and L. V. Crawford. 1979. T antigen is bound to a host protein in SV40-transformed cells. Nature 278:261-263.[CrossRef][Medline]
    66. 66
  66. Lednicky, J. A., and R. L. Garcea. 2000. Detection of SV40 DNA sequences in human tissue, p. 257-267. In L. Raptis (ed.), Methods in molecular biology, vol. 165. Humana Press, Totowa, N.J.
    67. 67
  67. Lednicky, J. A., R. L. Garcea, D. J. Bergsagel, and J. S. Butel. 1995. Natural simian virus 40 strains are present in human choroid plexus and ependymoma tumors. Virology 212:710-717.[CrossRef][Medline]
    68. 68
  68. Lednicky, J. A., A. R. Stewart, J. J. Jenkins, M. J. Finegold, and J. S. Butel. 1997. SV40 DNA in human osteosarcomas shows sequence variation among T-antigen genes. Int. J. Cancer 72:791-800.[CrossRef][Medline]
    69. 69
  69. Levine, A. J. 1993. The tumor suppressor genes. Annu. Rev. Biochem. 62:623-651.[CrossRef][Medline]
    70. 70
  70. Li, R. M., M. H. Branton, S. Tanawattanacharoen, R. A. Falk, J. C. Jennette, and J. B. Kopp. 2002. Molecular identification of SV40 infection in human subjects and possible association with kidney disease. J. Am. Soc. Nephrol. 13:2320-2330.[Abstract/Free Full Text]
    71. 71
  71. Linzer, D. I., and A. J. Levine. 1979. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell 17:43-52.[CrossRef][Medline]
    72. 72
  72. Malkin, D., S. Chilton-MacNeill, L. A. Meister, E. Sexsmith, L. Diller, and R. L. Garcea. 2001. Tissue-specific expression of SV40 in tumors associated with the Li-Fraumeni syndrome. Oncogene 20:4441-4449.[CrossRef][Medline]
    73. 73
  73. Martinelli, M., F. Martini, E. Rinaldi, L. Caramanico, E. Magri, E. Grandi, F. Carinci, A. Pastore, and M. Tognon. 2002. Simian virus 40 sequences and expression of the viral large T antigen oncoprotein in human pleomorphic adenomas of parotid glands. Am. J. Pathol. 161:1127-1133.[Abstract/Free Full Text]
    74. 74
  74. Martini, F., L. Iaccheri, L. Lazzarin, P. Carinci, A. Corallini, M. Gerosa, P. Iuzzolino, G. Barbanti-Brodano, and M. Tognon. 1996. SV40 early region and large T antigen in human brain tumors, peripheral blood cells, and sperm fluids from healthy individuals. Cancer Res. 56:4820-4825.[Abstract/Free Full Text]
    75. 75
  75. McCormick, F., and E. Harlow. 1980. Association of a murine 53,000-dalton phosphoprotein with simian virus 40 large-T antigen in transformed cells. J. Virol. 34:213-224.[Abstract/Free Full Text]
    76. 76
  76. Meinke, W., D. A. Goldstein, and R. A. Smith. 1979. Simian virus 40-related DNA sequences in a human brain tumor. Neurology 29:1590-1594.[Abstract/Free Full Text]
    77. 77
  77. Melnick, J. L., and S. Stinebaugh. 1962. Excretion of vacuolating SV-40 virus (papova virus group) after ingestion as a contaminant of oral poliovaccine. Proc. Soc. Exp. Biol. Med. 109:965-968.
    78. 78
  78. Mendoza, S. M., T. Konishi, and C. W. Miller. 1998. Integration of SV40 in human osteosarcoma DNA. Oncogene 17:2457-2462.[CrossRef][Medline]
    79. 79
  79. Monaco, M. C., P. N. Jensen, J. Hou, L. C. Durham, and E. O. Major. 1998. Detection of JC virus DNA in human tonsil tissue: evidence for site of initial viral infection. J. Virol. 72:9918-9923.[Abstract/Free Full Text]
    80. 80
  80. Monaco, M. C., J. Shin, and E. O. Major. 1998. JC virus infection in cells from lymphoid tissue. Dev. Biol. Stand. 94:115-122.[Medline]
    81. 81
  81. Monini, P., A. Rotola, D. Di Luca, L. De Lellis, E. Chiari, A. Corallini, and E. Cassai. 1995. DNA rearrangements impairing BK virus productive infection in urinary tract tumors. Virology 214:273-279.[CrossRef][Medline]
    82. 82
  82. Morris, J. A., K. M. Johnson, C. G. Aulisio, R. M. Chanock, and V. Knight. 1961. Clinical and serological responses in volunteers given vacuolating virus (SV40) by respiratory route. Proc. Soc. Exp. Biol. Med. 108:56-59.
    83. 83
  83. Mortimer, E. A., M. L. Lepow, E. Gold, F. C. Robbins, G. J. Burton, and J. F. Fraumeni. 1981. Long-term follow-up of persons inadvertently inoculated with SV40 as neonates. N. Engl. J. Med. 305:1517-1518.[Medline]
    84. 84
  84. Murakami, Y., C. R. Wobbe, L. Weissbach, F. B. Dean, and J. Hurwitz. 1986. Role of DNA polymerase alpha and DNA primase in simian virus 40 DNA replication in vitro. Proc. Natl. Acad. Sci. USA 83:2869-2873.[Abstract/Free Full Text]
    85. 85
  85. Pacini, F., A. Vivaldi, M. Santoro, M. Fedele, A. Fusco, C. Romei, F. Basolo, and A. Pinchera. 1998. Simian virus 40-like DNA sequences in human papillary thyroid carcinomas. Oncogene 16:665-669.[CrossRef][Medline]
    86. 86
  86. Padgett, B. L., and D. L. Walker. 1976. New human papovaviruses. Prog. Med. Virol. 22:1-35.[Medline]
    87. 87
  87. Padgett, B. L., and D. L. Walker. 1973. Prevalence of antibody in human sera against JC virus, an isolate from a case of progressive multifocal leukoencephalopathy. J. Infect. Dis. 127:467-470.[Medline]
    88. 88
  88. Padgett, B. L., D. L. Walker, G. M. ZuRhein, R. I. Eckroade, and B. H. Dessel. 1971. Cultivation of a papova-like virus from human brain with progressive multifocal leukoencephalopathy. Lancet i:1257-1260.
    89. 89
  89. Pagano, J. S. 2002. Viruses and lymphoma. N. Engl. J. Med. 347:89-94.[Abstract/Free Full Text]
    90. 90
  90. Pallas, D. C., L. K. Shahrik, B. L. Martin, S. Jaspers, T. B. Miller, D. L. Brautigan, and T. M. Roberts. 1990. Polyoma small and middle T antigens and SV40 small t antigen form stable complexes with protein phosphatase 2A. Cell 60:167-176.[CrossRef][Medline]
    91. 91
  91. Ponten, J., F. C. Jensen, and H. Koprowski. 1963. Morphological and virological investigation of human tissue cultures transformed with SV40. J. Cell. Comp. Physiol. 61:145-163.[CrossRef][Medline]
    92. 92
  92. Porcu, P., A. Ferber, Z. Pietrzkowski, C. T. Roberts, M. Adamo, D. LeRoith, and R. Baserga. 1992. The growth-stimulatory effect of simian virus 40 T antigen requires the interaction of insulin-like growth factor 1 with its receptor. Mol. Cell. Biol. 12:5069-5077.[Abstract/Free Full Text]
    93. 93
  93. Porras, A., S. Gaillard, and K. Rundell. 1999. The simian virus 40 small-t and large T antigens jointly regulate cell cycle reentry in human fibroblasts. J. Virol. 73:3102-3107.[Abstract/Free Full Text]
    94. 94
  94. Portolani, M., M. Borgatti, A. Corallini, E. Cassai, M. P. Grossi, and G. Barbanti-Brodano. 1978. Stable transformation of mouse, rabbit, and monkey cells and abortive transformation of human cells by BK virus, a human papovavirus. J. Gen. Virol. 38:369-374.[Abstract/Free Full Text]
    95. 95
  95. Rabson, A. S., G. T. O'Connor, L. Kirschstein, and W. L. Branigan. 1962. Papillary ependymomas produced in Rattus (mastomys) natalensis inoculated with vacuolating virus (SV40). J. Natl. Cancer Inst. 29:765-787.
    96. 96
  96. Ray, G. A., D. S. Peabody, J. L. Cooper, L. S. Cram, and P. M. Kraemer. 1990. SV40 T antigen alone drives karyotype instability that precedes neoplastic transformation of human diploid fibroblasts. J. Cell. Biochem. 42:13-31.[CrossRef][Medline]
    97. 97
  97. Reed, S. I., J. Ferguson, R. W. Davis, and C. R. Stark. 1975. T antigen binds to simian virus 40 DNA at the origin of replication. Proc. Natl. Acad. Sci. USA 72:1605-1609.[Abstract/Free Full Text]
    98. 98
  98. Reed, S. I., C. R. Stark, and J. C. Alwine. 1976. Autoregulation of simian virus 40 gene A by T antigen. Proc. Natl. Acad. Sci. USA 73:3083-3087.[Abstract/Free Full Text]
    99. 99
  99. Rizzo, P., M. Carbone, S. Fisher, C. Matker, L. J. Swinnen, A. Powers, I. Di Resta, S. Alkan, H. I. Pass, and R. I. Fisher. 1999. Simian virus 40 is present in most United States human mesotheliomas, but it is rarely present in non-Hodgkin's lymphoma. Chest 166:470S-473S.
    100. 100
  100. Rundell, K., and R. Parakati. 2001. The role of the SV40 ST antigen in cell growth promotion and transformation. Semin. Cancer Biol. 11:5-13.[CrossRef][Medline]
    101. 101
  101. Saenz-Robles, M. T., C. S. Sullivan, and J. M. Pipas. 2001. Transforming functions of simian virus 40. Oncogene 20:7899-7907.[CrossRef][Medline]
    102. 102
  102. Schell, T. D., and S. S. Tevethia. 2001. Control of advanced choroid plexus tumors in SV40 T antigen transgenic mice following priming of donor CD8(+) T lymphocytes by the endogenous tumor antigen. J. Immunol. 167:6947-6956.[Abstract/Free Full Text]
    103. 103
  103. Schell, T. D., and S. S. Tevethia. 2001. Cytotoxic T lymphocytes in SV40 infections. Methods Mol. Biol. 165:243-256.[Medline]
    104. 104
  104. Scherneck, S., M. Rudolph, E. Geissler, F. Vogel, L. Lubbe, H. Wahlte, G. Nisch, F. Weickman, and W. Zimmerman. 1979. Isolation of an SV-40 like papovavirus from human glioblastoma. Int. J. Cancer 24:523-531.[Medline]
    105. 105
  105. Sepulveda, A. R., M. J. Finegold, B. Smith, B. L. Slagle, J. L. DeMayo, R.-F. Shen, S. L. C. Woo, and J. S. Butel. 1989. Development of a transgenic mouse system for the analysis of stages in liver carcinogenesis using tissue-specific expression of SV40 large T-antigen controlled by regulatory elements of the human {alpha}-1-antitrypsin gene. Cancer Res. 49:6108-6117.[Abstract/Free Full Text]
    106. 106
  106. Shah, K., and N. Nathanson. 1976. Human exposure to SV40: review and comment. Am. J. Epidemiol. 103:1-12.[Free Full Text]
    107. 107
  107. Shah, K. V. 2000. Does SV40 infection contribute to the development of human cancers? Rev. Med. Virol. 10:31-43.[CrossRef][Medline]
    108. 108
  108. Shein, H. M., and J. F. Enders. 1962. Multiplication and cytopathogenicity of simian vacuolating virus 40 in cultures of human tissues. Proc. Soc. Exp. Biol. Med. 109:495-500.
    109. 109
  109. Shein, H. M., J. F. Enders, and J. D. Levinthal. 1962. Transformation induced by simian virus 40 in human renal cell cultures. II. Cell-virus relationships. Proc. Natl. Acad. Sci. USA 48:1350-1357.[Free Full Text]
    110. 110
  110. Shivapurkar, N., K. Harada, J. Reddy, R. H. Scheuermann, Y. Xu, R. W. McKenna, S. Milchgrub, S. H. Kroft, Z. Feng, and A. F. Gazdar. 2002. Presence of simian virus 40 DNA sequence in human lymphomas. Lancet 359:851-852.[CrossRef][Medline]
    111. 111
  111. Shivapurkar, N., T. Wiethege, I. I. Wishuba, E. Salomon, S. Milchgrub, K. M. Muller, A. Churg, H. I. Pass, and A. F. Gazdar. 1999. Presence of simian virus 40 sequences in malignant mesotheliomas and mesothelial cell proliferations. J. Cell. Biochem. 76:181-188.[CrossRef][Medline]
    112. 112
  112. Smale, S. T., and R. Tjian. 1986. T-antigen-DNA polymerase alpha complex implicated in simian virus 40 DNA replication. Mol. Cell. Biol. 6:4077-4087.[Abstract/Free Full Text]
    113. 113
  113. Small, J. A., G. Khoury, G. Jay, P. M. Howley, and G. A. Scangos. 1986. Early regions of JC virus and BK virus induce distinct and tissue-specific tumors in transgenic mice. Proc. Natl. Acad. Sci. USA 83:8288-8292.[Abstract/Free Full Text]
    114. 114
  114. Stahl, H., P. Droge, and R. Knippers. 1986. DNA helicase activity of SV40 large tumor antigen. EMBO J. 5:1939-1944.[Medline]
    115. 115
  115. Stratton, K., D. A. Almario, and M. C. McCormick (ed.). 2002. Immunization safety review: SV40 contamination of polio vaccine and cancer. National Academy Press, Washington, D.C.
    116. 116
  116. Strickler, H. D., J. J. Goedert, M. Fleming, W. D. Travis, A. E. Williams, C. S. Rabkin, R. W. Daniel, and K. V. Shah. 1996. Simian virus 40 and pleural mesothelioma in humans. Cancer Epidemiol. Biomark. Prev. 5:473-475.[Abstract]
    117. 117
  117. Sweet, B. H., and M. R. Hilleman. 1960. The vacuolating virus, SV40. Proc. Soc. Exp. Biol. Med. 105:420-427.
    118. 118
  118. Tabuchi, K., W. M. Kirsch, and M. Low. 1978. Screening of human brain tumors for SV40 related T antigen. Int. J. Cancer 21:12-17.[Medline]
    119. 119
  119. Taguchi, F., J. Kajioka, and T. Miyamura. 1982. Prevalence rate and age of acquisition of antibodies against JC virus and BK virus in human sera. Microbiol. Immunol. 26:1057-1064.[Medline]
    120. 120
  120. Tegtmeyer, P. 1972. Simian virus 40 deoxyribonucleic acid synthesis: the viral replicon. J. Virol. 10:591-598.[Abstract/Free Full Text]
    121. 121
  121. Tegtmeyer, P., M. Schwartz, J. K. Collins, and K. Rundell. 1975. Regulation of tumor antigen synthesis by simian virus 40 gene A. J. Virol. 16:168-178.[Abstract/Free Full Text]
    122. 122
  122. Testa, J. R., M. Carbone, A. Hirvonen, K. Khalili, B. Krynska, K. Linnainmaa, F. D. Poley, P. Rizzo, V. Rusch, and G.-H. Xiao. 1998. A multi-institutional study confirms the presence and expression of simian virus 40 in human malignant mesotheliomas. Cancer Res. 58:4505-4509.[Abstract/Free Full Text]
    123. 123
  123. Tjian, R. 1978. The binding site on SV40 DNA for a T antigen-related protein. Cell 13:165-179.[CrossRef][Medline]
    124. 124
  124. Van Dyke, T. A., C. Finalay, D. Miller, J. Marks, G. Lozano, and A. J. Levine. 1987. Relationship between simian virus 40 large tumor antigen expression and tumor formation in transgenic mice. J. Virol. 61:2029-2032.[Abstract/Free Full Text]
    125. 125
  125. Vilchez, R. A., C. R. Madden, C. A. Kozinetz, S. J. Halvorson, Z. S. White, J. L. Jorgensen, C. J. Finch, and J. S. Butel. 2002. Association between simian virus 40 and non-Hodgkin lymphoma. Lancet 359:817-823.[CrossRef][Medline]
    126. 126
  126. Waheed, I., Z. S. Guo, G. A. Chen, T. S. Weiser, D. M. Nguyen, and D. S. Schrump. 1999. Antisense to SV40 early gene region induces growth arrest and apoptosis in T-antigen-positive human pleural mesothelioma cells. Cancer Res. 59:6068-6073.[Abstract/Free Full Text]
    127. 127
  127. Walker, D. L., B. L. Padgett, G. M. ZuRhein, A. E. Albert, and R. F. Marsh. 1973. Induction of brain tumors in hamsters. Science 181:674-676.[Abstract/Free Full Text]
    128. 128
  128. Weggen, S., T. A. Bayer, A. von Deimling, G. Reifenberger, D. von Schweinitz, O. D. Wiestler, and T. Pietsch. 2000. Low frequency of SV40, JC and BK polyomavirus sequences in human medulloblastomas, meningiomas, and ependymomas. Brain Pathol. 10:85-92.[Medline]
    129. 129
  129. Yamamoto, H., T. Nakayama, H. Murakami, T. Hosaka, T. Nakamata, T. Tsuboyama, M. Oka, T. Nakamura, and J. Toguchida. 2000. High incidence of SV40-like sequence detection in tumour and peripheral blood cells of Japanese osteosarcoma patients. Br. J. Cancer 82:1677-1681.[CrossRef][Medline]
    130. 130
  130. Yu, J., A. Boyapati, and K. Rundell. 2001. Critical role for SV40 small-t antigen in human cell transformation. Virology 290:192-198.[CrossRef][Medline]
    131. 131
  131. zur Hausen, H. 1987. Papillomaviruses in human cancer. Cancer 59:1692-1696.[CrossRef][Medline]
    132. 132
  132. Zu Rhein, G. 1983. Studies of JC virus-induced nervous system tumors in the Syrian hamster: a review. Prog. Clin. Biol. Res. 105:205-221.[Medline]

Journal of Virology, May 2003, p. 5039-5045, Vol. 77, No. 9
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.9.5039-5045.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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