Specific antibodies reacting with simian virus 40 capsid protein mimotopes in serum samples from healthy blood donors

Proc. Natl. Acad. Sci. U.S.A.

Cristaudo

et al. 2012

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Human malignant pleural mesothelioma (MPM) is considered a rare tumor, but recent estimations indicate that one-quarter million people will die of this neoplasm in Europe in the next three decades. The mineral asbestos is considered the main causative agent of this neoplasm. MPM is largely unresponsive to conventional chemotherapy/radiotherapy. In addition to asbestos exposure, genetic predisposition to asbestos carcinogenesis and to simian virus (SV) 40 infection has also been suggested. SV40 is a DNA tumor virus found in some studies to be associated at high prevalence with MPM. SV40 sequences have also been detected, although at a lower prevalence than in MPM, in blood specimens from healthy donors. However, some studies have failed to reveal SV40 footprints in MPM and its association with this neoplasm. These conflicting results indicate the need for further investigations with new approaches. We report on the presence of antibodies in serum samples from patients affected by MPM that specifically react with two different SV40 mimotopes. The two SV40 peptides used in indirect ELISAs correspond to viral capsid proteins. ELISA with the two SV40 mimotopes gave overlapping results. Our data indicate that in serum samples from MPM-affected patients (n = 97), the prevalence of antibodies against SV40 viral capsid protein antigens is significantly higher (26%, P = 0.043) than in the control group (15%) represented by healthy subjects (n = 168) with the same median age (66 y) and sex. Our results suggest that SV40 is associated with a subset of MPM and circulates in humans.antibody | neoplasia

Section: Resultsmentioning

confidence: 99%

Section: Sv40 Mimotopesmentioning

confidence: 99%

Section: Sv40 Mimotopesmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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High prevalence of serum antibodies reacting with simian virus 40 capsid protein mimotopes in patients affected by malignant pleural mesothelioma

Mazzoni¹,

Proc. Natl. Acad. Sci. U.S.A.

Cristaudo

et al. 2012

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Significant association between human osteosarcoma and simian virus 40

Mazzoni

Benassi

et al. 2014

Cancer

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BACKGROUND:Simian virus 40 (SV40) has been considered to be an oncogenic viral agent in the development of osteosarcoma (OS), which to the authors' knowledge continues to be of unknown etiology. METHODS: In the current study, serum samples from patients with OS were investigated with an indirect enzyme-linked immunoadsorbent assay (ELISA) to test for the presence of immunoglobulin G antibodies, which react with SV40 antigens. In ELISA, SV40 antigens were represented by 2 synthetic polypeptides that mimic epitopes of the viral capsid proteins 1 to 3. Additional sera from patients with breast cancer and undifferentiated nasopharyngeal carcinoma as well as healthy subjects were the controls. RESULTS: Immunologic results suggested that antibodies that react with SV40 mimotopes were more prevalent (44%) in serum samples from patients with OS compared with healthy subjects (17%). The difference in prevalence between these cohorts was statistically significant (P<.001). It is interesting to note that in the patients with OS, significance indicated the difference between OS versus breast cancer (44% vs 15%; P<.001) and OS versus undifferentiated nasopharyngeal carcinoma (44% vs 25%; P<.05). CONCLUSIONS: The data from the current study indicate an association between OS and SV40. These data could be transferred to clinical applications for innovative therapies to address SV40-positive OS. Cancer 2015;121:708-15. V C 2014 American Cancer Society.KEYWORDS: osteosarcoma, simian virus 40 (SV40), antibody, viral agent. INTRODUCTIONHuman osteosarcoma (OS) is a rare malignant neoplasm of the bone that for the most part affects children and young adolescents.1 To the best of our knowledge, little is known regarding the biology and pathology of this bone tumor. Cellular and animal experimental models were used in an attempt to elucidate the mechanism of OS onset.2-5 OS has multiple genetic risk factors, including groups of genes involved in cell proliferation/cell cycle/DNA damage repair. It has been reported that the incidence of OS is increased significantly in patients with specific hereditary diseases.

Immunologic evidence of a strong association between non‐Hodgkin lymphoma and simian virus 40

Tognon

Luppi

et al. 2015

Cancer

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BACKGROUND: Non-Hodgkin lymphoma (NHL), the most common cancer of the lymphatic system, is of unknown etiology. The identification of etiologic factors in the onset of NHL is a key event that could facilitate the prevention and cure of this malignancy. Simian virus 40 (SV40) has been considered an oncogenic agent in the onset/progression of NHL. METHODS: In this study, an indirect enzyme-linked immunosorbent assay with 2 synthetic peptides that mimic SV40 antigens of viral capsid proteins 1 to 3 was employed to detect specific antibodies against SV40. Serum samples were taken from 2 distinct cohorts of NHL-affected patients (NHL1 [n 5 89] and NHL2 [n 5 61]) along with controls represented by oncologic patients affected by breast cancer (BC; n 5 78) and undifferentiated nasopharyngeal carcinoma (UNPC; n 5 64) and 3 different cohorts of healthy subjects (HSs; HS1 [n 5 130], HS2 [n 5 83], and HS3 [n 5 87]). RESULTS: Immunologic data indicated that in serum samples from NHL patients, antibodies against SV40 mimotopes were detectable with a prevalence of 40% in NHL1 patients and with a prevalence of 43% in NHL2 patients. In HSs of the same median age as NHL patients, the prevalence was 16% for the HS1 group (57 years) and 14% for the HS2 group (65 years). The difference was statistically significant (P <.0001 and P <.001). Interestingly, the difference between NHL1/NHL2 patients and BC patients (40%/43% vs 15%, P <.001) and between NHL1/NHL2 patients and UNPC patients (40%/43% vs 25%, P <.05) was significant. CON-CLUSIONS: Our data indicate a strong association between NHL and SV40 and thus a need for innovative therapeutic approaches for this hematologic malignancy.