scholarly journals Investigation of the SV40 – Human Cancer Association: Look for the Full Signature of the Virus

2001 ◽  
Vol 17 (3) ◽  
pp. 159-161 ◽  
Author(s):  
Keerti V. Shah ◽  
Dana E. M. Rollison
Keyword(s):  
Risk Factors ◽  
Tumor Cell ◽  
Cancer Patients ◽  
Sensitivity And Specificity ◽  
Human Cancer ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Viral Integration ◽  
Human Community ◽  
Sv40 Infection

In the controversy about the association of simian virus 40 with human cancers, the greatest problem is the ascertainment of SV40 exposure. This difficulty would be resolved if one were to look for all components of SV40 infection. How does SV 40 circulate in the human community? Do cancer patients with SV40-positive tumors have serological correlates of SV 40 infection and of SV40-induced cancer? SV40 association with a cancer should be studied in the context of the known risk factors for that cancer. The tumor cell-virus relationship should be characterized with respect to viral integration and viral localization to the tumor cell. Specimens should be masked and the assays should include panels of specimens to estimate analytic sensitivity and specificity. In view of the rarity of some of the tumors reported to be associated with SV40, a multi-institutional investigation initiated and coordinated by the NIH would be most effective.

Is There a Role for SV40 in Human Cancer?

2006 ◽  
Vol 24 (26) ◽  
pp. 4356-4365 ◽  
Author(s):  
Danielle L. Poulin ◽  
James A. DeCaprio
Keyword(s):  
Human Cancer ◽  
Simian Virus 40 ◽  
The United States ◽  
Simian Virus ◽  
Human Tumors ◽  
Direct Role ◽  
Potential Health ◽  
Polio Vaccination ◽  
Sv40 Infection ◽  
Positive Correlations

The question of whether Simian Virus 40 (SV40) can cause human tumors has been one of the most highly controversial topics in cancer research during the last 50 years. The longstanding debate began with the discovery of SV40 as a contaminant in poliovirus vaccine stocks that were used to inoculate approximately 100 million children and adults in the United States between 1955 and 1963, and countless more throughout the world. Concerns regarding the potential health risk of SV40 exposure were reinforced by studies demonstrating SV40's potential to transform human cells and promote tumor growth in animal models. Many studies have attempted to assess the relationship between the potential exposure of humans to SV40 and cancer incidence. Reports of the detection of SV40 DNA in a variety of cancers have raised serious concerns as to whether the inadvertent inoculation with SV40 has led to the development of cancer in humans. However, inconsistent reports linking SV40 with various tumor types has led to conflicting views regarding the potential of SV40 as a human cancer virus. Several recent studies suggest that older detection methodologies were flawed, and the limitations of these methods could account for most, if not all, of the positive correlations of SV40 in human tumors to date. Although many people may have been exposed to SV40 by polio vaccination, there is inadequate evidence to support widespread SV40 infection in the population, increased tumor incidence in those individuals who received contaminated vaccine, or a direct role for SV40 in human cancer.

scholarly journals N-Glycolyl GM1 Ganglioside as a Receptor for Simian Virus 40

2007 ◽  
Vol 81 (23) ◽  
pp. 12846-12858 ◽  
Author(s):  
Maria A. Campanero-Rhodes ◽  
Alicia Smith ◽  
Wengang Chai ◽  
Sandro Sonnino ◽  
Laura Mauri ◽  
...  
Keyword(s):  
Simian Virus 40 ◽  
High Specificity ◽  
Simian Virus ◽  
Receptor Expression ◽  
Host Cells ◽  
Gm1 Ganglioside ◽  
Ganglioside Gm1 ◽  
Virus Binding ◽  
Host Interactions ◽  
Sv40 Infection

ABSTRACT Carbohydrate microarrays have emerged as powerful tools in analyses of microbe-host interactions. Using a microarray with 190 sequence-defined oligosaccharides in the form of natural glycolipids and neoglycolipids representative of diverse mammalian glycans, we examined interactions of simian virus 40 (SV40) with potential carbohydrate receptors. While the results confirmed the high specificity of SV40 for the ganglioside GM1, they also revealed that N-glycolyl GM1 ganglioside [GM1(Gc)], which is characteristic of simian species and many other nonhuman mammals, is a better ligand than the N-acetyl analog [GM1(Ac)] found in mammals, including humans. After supplementing glycolipid-deficient GM95 cells with GM1(Ac) and GM1(Gc) gangliosides and the corresponding neoglycolipids with phosphatidylethanolamine lipid groups, it was found that GM1(Gc) analogs conferred better virus binding and infectivity. Moreover, we visualized the interaction of NeuGc with VP1 protein of SV40 by molecular modeling and identified a conformation for GM1(Gc) ganglioside in complex with the virus VP1 pentamer that is compatible with its presentation as a membrane receptor. Our results open the way not only to detailed studies of SV40 infection in relation to receptor expression in host cells but also to the monitoring of changes that may occur with time in receptor usage by the virus.

scholarly journals Simian virus 40 and cancer

2011 ◽  
pp. 131-140
Author(s):  
Sandra Eliasz ◽  
Michele Carbone ◽  
Maurizio Bocchetta
Keyword(s):  
Molecular Biology ◽  
Human Population ◽  
Animal Studies ◽  
Cell Transformation ◽  
Human Cancer ◽  
Mesothelial Cell ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Oncogenic Virus ◽  
Experimental Approaches

Since its discovery in 1960 as a contaminant of poliovaccines, Simian Virus 40 (SV40) has been the object of extensive studies to assess whether this oncogenic virus plays a role in human carcinogenesis. Over the last two decades, this question has met with broad scepticism. However, there is increasing evidence linking SV40 to specific types of human cancer, especially malignant mesothelioma. Recently, two laboratories using different experimental approaches independently confirmed that SV40 acts synergistically with environmental fibers to promote mesothelial cell transformation and mesothelioma. Most of the scepticism concerning SV40 and cancer was due to the lack of clear epidemiologic data. However, it is still not clear how SV40 circulates in the human population, making the identification of SV40-exposed versus non-exposed cohorts problematic. Consequently, the most helpful insights into SV40-mediated carcinogenesis have come from molecular pathology, cell and molecular biology, and from animal studies.

African Green Monkey Fibroblast Action Morphology during SV40 Infection

1977 ◽  
Vol 32 (5-6) ◽  
pp. 409-412
Author(s):  
Gerhard Brandner ◽  
Myung-Sam Cho
Keyword(s):  
Tumor Antigen ◽  
Actin Filaments ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
African Green Monkey ◽  
Skin Fibroblasts ◽  
Focus Formation ◽  
Normal Morphology ◽  
Green Monkey ◽  
Sv40 Infection

Abstract Monkey skin fibroblasts were infected with simian virus 40. Cells that exhibited the viral tumor antigen were found to retain the normal morphology of actin filaments up to six days after infection. However when cells were transformed in terms of focus formation they had lost the normal actin morphology.

scholarly journals Pairs of Vp1 Cysteine Residues Essential for Simian Virus 40 Infection

2005 ◽  
Vol 79 (6) ◽  
pp. 3859-3864 ◽  
Author(s):  
Peggy P. Li ◽  
Akira Nakanishi ◽  
Vanessa Fontanes ◽  
Harumi Kasamatsu
Keyword(s):  
Nuclear Localization ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Dominant Negative ◽  
Capsid Proteins ◽  
Cysteine Residues ◽  
Nuclear Trafficking ◽  
Virion Assembly ◽  
Capsid Protein Vp1 ◽  
Sv40 Infection

ABSTRACT Transient disulfide bonding occurs during the intracellular folding and pentamerization of simian virus 40 (SV40) major capsid protein Vp1 (P. P. Li, A. Nakanishi, S. W. Clark, and H. Kasamatsu, Proc. Natl. Acad. Sci. USA 99:1353-1358, 2002). We investigated the requirement for Vp1 cysteine pairs during SV40 infection. Our analysis identified three Vp1 double-cysteine mutant combinations that abolished viability as assayed by plaque formation. Mutating the Cys49-Cys87 pair or the Cys87-Cys254 pair led to ineffective nuclear localization and diminished accumulation of the mutant Vp1s, and the defect extended in a dominant-negative manner to the wild-type minor capsid proteins Vp2/3 and an affinity-tagged recombinant Vp1 expressed in the same cells. Mutating the Cys87-Cys207 pair preserved the nuclear localization and normal accumulation of the capsid proteins but diminished the production of virus-like particles. Our results are consistent with a role for Cys49, Cys87, and Cys254 in the folding and cytoplasmic-nuclear trafficking of Vp1 and with a role for Cys87 and Cys207 in the assembly of infectious particles. These findings suggest that transient disulfide bond formation between certain Vp1 cysteine residues functions at two stages of SV40 infection: during Vp1 folding and oligomerization in the cytoplasm and during virion assembly in the nucleus.

scholarly journals Tumorigenicity of simian virus 40-hepatocyte cell lines: effect of in vitro and in vivo passage on expression of liver-specific genes and oncogenes.

1988 ◽  
Vol 8 (10) ◽  
pp. 4492-4501 ◽  
Author(s):  
C D Woodworth ◽  
J W Kreider ◽  
L Mengel ◽  
T Miller ◽  
Y L Meng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Cell ◽  
Cell Lines ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Tumor Cell Lines ◽  
Glutathione S Transferase

Five simian virus 40 (SV40)-hepatocyte cell lines were examined for tumorigenicity and the effect of in vitro passage on the expression of four liver-specific genes (albumin, transferrin, alpha 1-antitrypsin, and phosphoenolpyruvate carboxykinase), two oncogenes (c-Ha-ras and c-raf), and two genes associated with hepatocarcinogenesis (alpha-fetoprotein and placental-type glutathione-S-transferase). At low passage (12 to 22), all five cell lines expressed the four liver-specific genes at levels similar to those in the liver and were not tumorigenic or were weakly tumorigenic. At high passage (33 to 61), the cell lines formed carcinomas, and four out of five cell lines produced primary tumors that metastasized. At least two cell lines produced well-differentiated hepatocellular carcinomas that expressed liver-specific RNAs. Levels of expression of liver-specific genes changed with time in culture. Some of the changes in liver-specific gene expression in the tumor tissue (such as for the phosphoenolpyruvate carboxykinase gene) paralleled those that occurred with in vitro passage, while other changes (such as for the albumin gene) did not parallel those that occurred with in vitro passage. Correlations between enhanced expression of c-Ha-ras and tumorigenic potential and between the process of SV40 immortalization and induced expression of c-raf and glutathione-S-transferase-P were observed. Induction of alpha-fetoprotein was detected with in vitro and in vivo passage only in the CWSV14 cell line and was paralleled by diminished albumin expression. In conclusion, we developed a model system with five SV40-hepatocyte cell lines, tumors induced by them, and tumor cell lines to examine changes in gene expression that accompany the progression from a normal cell to a hepatocellular carcinoma. Because the SV40-hepatocyte cell lines and tumor cell lines remain highly differentiated and vary in the magnitude of expression of specific genes, they can be used to study the molecular mechanisms regulating gene expression, in particular those regulating specific genes associated with differentiation.

Simian virus 40(SV40) and human cancer: a review of the serological data

2004 ◽  
Vol 14 (4) ◽  
pp. 231-239 ◽  
Author(s):  
Keerti V. Shah ◽  
Denise A. Galloway ◽  
Wendy A. Knowles ◽  
Raphael P. Viscidi
Keyword(s):  
Human Cancer ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Serological Data

scholarly journals Patterns of polyadenylation site selection in gene constructs containing multiple polyadenylation signals.

1988 ◽  
Vol 8 (11) ◽  
pp. 4829-4839 ◽  
Author(s):  
R M Denome ◽  
C N Cole
Keyword(s):  
Simian Virus 40 ◽  
Simian Virus ◽  
Polyadenylation Signal ◽  
Coding Region ◽  
S1 Nuclease ◽  
Cytoplasmic Rna ◽  
Sv40 Origin ◽  
Sv40 Infection ◽  
Simplex Virus ◽  
Polyadenylation Signals

We have constructed a series of plasmids containing multiple polyadenylation signals downstream of the herpes simplex virus type 1 (HSV) thymidine kinase (tk)-coding region. The signals used were from the simian virus 40 (SV40) late gene, the HSV tk gene, and an AATAAA-containing segment of the SV40 early region. This last fragment signals polyadenylation poorly in our constructs and not at all during SV40 infection. All plasmids contained the SV40 origin of replication. Plasmids were transfected into Cos-1 cells; after 48 h, cytoplasmic RNA was isolated and the quantity and 3'-end structure of tk mRNAs was analyzed by using S1 nuclease protection assays. In all constructs, all polyadenylation signals were used. Increasing the number of poly(A) signals 3' to the tk-coding region did not affect the total amount of polyadenylated RNA produced, even with the weakest signal. Increasing the distance between two signals caused an increase in the use of the 5' signal and a decrease in the use of the 3' signal. Changing the distance between the 5' cap and first signal did not affect signal use. Analyses of cytoplasmic mRNA stability, nuclear RNA distribution, and transcription in the polyadenylation signal region indicated that the distribution of tk RNAs ending at different poly(A) sites was the result of poly(A) signal choice, not other aspects of RNA metabolism. Four possible mechanisms of polyadenylation signal recognition are discussed.

Sign in / Sign up

Export Citation Format

Share Document