SV40 - Simian Vacuolating virus 40


SV40 is an abbreviation for simian vacuolating virus 40 or simian virus 40, a polyomavirus that is found in both monkeys and humans. Like other polyomaviruses, SV40 is a DNA virus that has the potential to cause tumors in animals, but most often persists as a latent infection

The discovery of SV40 revealed that between 1955 and 1963 around 90% of children and 60% of adults in the U.S. were inoculated with SV40-contaminated polio vaccines.[3]

SV40 was first identified by Ben Sweet and Maurice Hilleman in 1960 when they found that between 10-30% of polio vaccines in the USA were contaminated with SV40.[24] In 1962, Bernice Eddy described the SV40 oncogenic function inducing sarcoma and ependymomas in hamsters inoculated with monkeys cells infected with SV40.[25] The complete viral genome was sequenced by Fiers and his team at the University of Ghent (Belgium) in 1978.[26]


"Poliovaccines were produced in kidney cell cultures derived from rhesus, green, and patas monkeys (reviewed in Ref. 2 ). Rhesus monkeys are natural hosts of SV40, and, in captivity, related species caged with infected animals, including the cynomolgus macaque and African green monkey, are also easily infected (2) . SV40 infection appears harmless in immunocompetent hosts, indicating that monkeys carrying the virus showed no obvious signs of illness and thus were not excluded for use in vaccine production. Thus, it has been estimated that millions of people worldwide were inadvertently exposed to SV40 through contaminated vaccines administered from 1955 to 1963 (reviewed in Refs. 123 ). Similar to poliovaccines, adenovaccines 3 and 7 distributed to a limited extent among military and civilian personnel between 1961 and 1965 were shown to contain SV40 sequences (4) .

Soon after its discovery, SV40 was shown to be an oncogenic papovavirus that is capable of inducing tumors in hamsters, mastomys, and some strains of mice and of transforming human cells in tissue culture. Recently, SV40 DNA sequences have been detected in several human tumor types, including mesotheliomas, ependymomas, and osteosarcomas (reviewed in Refs. 2 and 3 ).

Transl Lung Cancer Res. 2020 Feb;9(Suppl 1):S47-S59. doi: 10.21037/tlcr.2020.02.03.

SV40 and human mesothelioma.

Carbone M1, Gazdar A2, Butel JS3.

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Simian virus 40 (SV40) is a DNA tumor virus capable of infecting and transforming human mesothelial (HM) cells in vitro. Hamsters injected intracardially to expose most tissue types to SV40 preferentially develop mesotheliomas. In humans, asbestos is the main cause of mesothelioma, and asbestos and SV40 are co-carcinogens in transforming HM cells in tissue culture and in causing mesothelioma in hamsters. Laser microdissection experiments conducted in the laboratory of Adi Gazdar demonstrated that SV40 was present specifically in the malignant mesothelioma cells and not in nearby stromal cells. Further experiments demonstrated that SV40 remains episomal in HM cells and astrocytes because of the production of a long antisense RNA that represses viral capsid protein production. Thus, the potent SV40 oncoprotein, T-antigen (Tag), is expressed, but because the capsid proteins are not produced, the cells are not lysed and, instead, become transformed. Together this evidence suggests that SV40 may contribute to the development of mesotheliomas in humans. However, epidemiological evidence to support this hypothesis is lacking. This chapter also summarizes the introduction of SV40, a monkey virus, into the human population as an unrecognized contaminant of early poliovaccines. In addition to mesotheliomas, SV40 now is linked with brain cancers, osteosarcomas, and lymphomas in humans. Explanations are provided for the apparent geographic variations in SV40 prevalence and for controversies about the role of SV40 in human cancer.

mSphere. 2020 Mar 18;5(2). pii: e00187-20. doi: 10.1128/mSphere.00187-20.

In Support of Simian Polyomavirus 40 VP4 as a Later Expressed Viroporin.

Daniels R1, Hebert DN2.

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Simian virus 40 VP4 was discovered in 2007 as a later expressed viral protein initiated from a downstream Met on the VP2/VP3 transcript. VP4's role as a viroporin involved in viral release was supported in a series of additional articles that characterized the ability of VP4 to associate with and permeabilize biological membranes. This commentary is our response to the perspective from Henriksen and Rinaldo (mSphere 5:e00019-20, 2020, https://doi.org/10.1128/mSphere.00019-20) that challenges the existence of SV40 VP4.

J Cell Physiol. 2020 Jul;235(7-8):5847-5855. doi: 10.1002/jcp.29533. Epub 2020 Feb 3.

Specific antibodies reacting to JC polyomavirus capsid protein mimotopes in sera from multiple sclerosis and other neurological diseases-affected patients.

Mazzoni E1, Bononi I1, Pietrobon S1, Torreggiani E1, Rossini M1, Pugliatti M2, Casetta I2, Castellazzi M2, Granieri E2, Guerra G3, Martini F1, Tognon M1.

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Published data support the hypothesis that viruses could be trigger agents of multiple sclerosis onset. This link is based on evidence of early exposure to viral agents in patients affected by this neurologic disease. JC (JC polyomavirus [JCPyV]), BK (BKPyV), and simian virus 40 (SV40) neurotropic polyomavirus footprints have been detected in brain tissue specimens and samples from patients affected by different neurological diseases. In this investigation, serum samples from patients affected by multiple sclerosis and other inflammatory and noninflammatory neurologic diseases, as well as healthy subjects representing the control, were investigated for immunoglobulin G (IgG) antibodies against JCPyV. To this end, an immunologic approach was employed, which consists of employing indirect enzyme-linked immunosorbent assay testing with synthetic peptides mimicking viral capsid protein 1 antigens. A significantly lower prevalence of IgG antibodies against JCPyV VP1 epitopes, with a low titer, was detected in serum samples from patients with multiple sclerosis (MS) and other neurologic diseases than in healthy subjects. Our study indicates that the prevalence of JCPyV antibodies from patients with multiple sclerosis is 50% lower than in healthy subjects, suggesting specific immune impairments. These results indicate that patients affected by neurological diseases, including MS, respond poorly to JCPyV VP1 antigens, suggesting specific immunologic dysfunctions.

J Virol. 2020 Mar 11. pii: JVI.00103-20. doi: 10.1128/JVI.00103-20. [Epub ahead of print]

Ubqln4 facilitates ER-to-cytosol escape of a nonenveloped virus during infection.

Liu X1, Tsai B2.

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The nonenveloped polyomavirus SV40 must penetrate the host endoplasmic reticulum (ER) membrane to enter the cytosol in order to promote infection. How this is accomplished is not entirely clear. Here we demonstrate that the cytosolic chaperone Ubiquilin4 (Ubqln4) binds directly to the ER membrane J proteins B12 and B14. Strategically localized at the ER-cytosol interface, Ubqln4 captures SV40 emerging from the ER, thereby facilitating ER escape of the virus into the cytosol that leads to infection. Strikingly, Ubqln4 engages the J proteins in a J-domain-independent manner, in contrast to the previously reported Hsc70-Hsp105-SGTA-Bag2 cytosolic complex that also mediates SV40 ER-to-cytosol transport. Our results also reveal that the H domain and STI1 motif (1, 2) of Ubqln4 support J protein-binding essential for SV40 infection. Together, these data further clarify the molecular basis by which a nonenveloped virus escapes a host membrane during infectious entry. How a nonenveloped virus escapes from a host membrane to promote infection remains an enigmatic process. In the case of the nonenveloped polyomavirus SV40, penetration of the ER membrane to reach the cytosol is a decisive virus infection step. In this study, we found a new host factor called Ubqln4 that facilitates escape of SV40 from the ER into the cytosol, thereby providing a path for the virus to enter the nucleus to cause infection.

Cancer Immunol Immunother. 2020 Apr 20. doi: 10.1007/s00262-020-02570-3. [Epub ahead of print]

Epstein-Barr virus (EBV) and polyomaviruses are detectable in oropharyngeal cancer and EBV may have prognostic impact.

Carpén T1,2, Syrjänen S3, Jouhi L4, Randen-Brady R5, Haglund C6,7, Mäkitie A4,8,9, Mattila PS4, Hagström J5,7,10.

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The etiological role of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OPSCC) is confirmed. However, the role of other oncoviruses in OPSCC is unknown.


A total of 158 consecutive OPSCC patients treated with curative intent were included. DNA extracted from tumor sections was used to detect Epstein-Barr virus (EBV), HPV, and the following polyomaviruses: John Cunningham virus (JCV), Simian virus 40 (SV40), and BK virus (BKV) with PCR. In addition, p16 expression was studied by immunohistochemistry, and EBV-encoded small RNA (EBER) transcripts were localized by in situ hybridization. The effect of viral status on overall survival (OS) and disease-free survival (DFS) was analyzed.


A total of 94/158 samples (59.5%) were HPV-positive, 29.1% contained BKV DNA, 20.3% EBV DNA, 13.9% JCV DNA, and 0.6% SV40 DNA. EBER was expressed only in stromal lymphocytes adjacent to the tumor and correlated with HPV positivity (p = 0.026). p16 expression associated only with HPV. None of the three polyomaviruses had an impact on survival. Patients with EBER-positive but HPV-negative OPSCC had significantly poorer OS and DFS than those with HPV-positive OPSCC and slightly worse prognosis compared with the patients with EBER-negative and HPV-negative OPSCC.


Polyomaviruses are detectable in OPSCC but seem to have no impact on survival, whereas HPV was the strongest viral prognostic factor. EBER expression, as a sign of latent EBV infection, may have prognostic impact among patients with HPV-negative OPSCC. EBER analysis may identify a new subgroup of OPSCCs unrelated to HPV.

Neuropathology. 2019 Dec;39(6):467-473. doi: 10.1111/neup.12599. Epub 2019 Oct 4.

Progressive multifocal leukoencephalopathy in idiopathic CD4+ lymphocytopenia: A case report and review of literature.

Aggarwal D1, Tom JP1, Chatterjee D1, Goyal M2.

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Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease due to a lytic infection of oligodendrocytes caused by polyoma virus (JC virus) infection. PML usually occurs in a setting of severe immunosuppression and is most commonly associated with human immunodeficiency virus (HIV) infection. Idiopathic CD4+ lymphocytopenia is a very rare cause of PML and only a few cases have been reported in the literature. We present a case of a 45-year-old man who presented with behavioral alteration followed by progressive weakness of right side of the body. Contrast-enhanced magnetic resonance imaging of the brain revealed confluent irregular areas of T2-weighted/fluid-attenuated inversion recovery hyperintensities in left frontoparietal and right temporoparietal regions. His hematological work up showed a decreased absolute CD4+ count of 217 per microliter, but was negative for HIV serology. Keeping a differential diagnoses of central nervous system lymphoma, brain biopsy was performed. Histopathology revealed demyelination with presence of intranuclear inclusions in the oligodendrocytes, which were positive for SV40 immunostain. Adjacent areas showed reactive gliosis with hypertrophic astrocytes, hence a diagnosis of PML was made. The patient died due to aspiration pneumonia. PML can occur very rarely in association with idiopathic CD4+ lymphocytopenia in the absence of other immunosuppressive illnesses. This report highlights the importance of high index of clinical suspicion and need for a careful histological examination for diagnosis of PML to facilitate adequate patient management.

J Neurovirol. 2010 Mar;16(2):141-9. doi: 10.3109/13550281003685839.

Association of autism with polyomavirus infection in postmortem brains.

Lintas C1, Altieri LLombardi FSacco RPersico AM.

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Autism is a highly heritable behavioral disorder. Yet, two decades of genetic investigation have unveiled extremely few cases that can be solely explained on the basis of de novo mutations or cytogenetic abnormalities. Vertical viral transmission represents a nongenetic mechanism of disease compatible with high parent-to-offspring transmission and with low rates of disease-specific genetic abnormalities. Vertically transmitted viruses should be found more frequently in the affected tissues of autistic individuals compared to controls. Our initial step was thus to assess by nested polymerase chain reaction (PCR) and DNA sequence analysis the presence of cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus type 1 (HSV1), herpes simplex virus type 2 (HSV2), human herpes virus 6 (HHV6), BK virus (BKV), JC virus (JCV), and simian virus 40 (SV40) in genomic DNA extracted from postmortem temporocortical tissue (Brodmann areas 41/42) belonging to 15 autistic patients and 13 controls. BKV, JCV, and SV40 combined are significantly more frequent among autistic patients compared to controls (67% versus 23%, respectively; P < .05). The majority of positives yielded archetypal sequences, whereas six patients and two controls unveiled single-base pair changes in two or more sequenced clones. No association is present with the remaining viruses, which are found in relatively few individuals (N <or= 3). Also polyviral infections tend to occur more frequently in the brains of autistic patients compared to controls (40% versus 7.7%, respectively; P = .08). Follow-up studies exploring vertical viral transmission as a possible pathogenetic mechanism in autistic disorder should focus on, but not be limited to, the role of polyomaviruses.

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