Different simian virus 40 genomic regions and sequences homologous with SV40 large T antigen in DNA of human brain and bone tumors and of leukocytes from blood donors

Martini, Fernanda; Lazzarin, L; Iaccheri, Laura; Vignocchi, Beatrice; Finocchiaro, Gaetano; Magnani, Ivana; Serra, Massimo; Scotlandi, Katia; Barbanti‐Brodano, Giuseppe; Tognon, Mauro

doi:10.1002/cncr.10272

Cited by 64 publications

(44 citation statements)

References 52 publications

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“…Some epidemiologic data suggest that SV40 could spread through contact in the familial environment or schools. SV40 footprints have been detected in stool, urine, tonsil, and blood specimens from children and adults, and this suggests that different routes of transmission are responsible for SV40 infection . In agreement with this result, specific antibodies against SV40 have been revealed by different methods in sera from normal children, adults, and elderly subjects …”

Section: Discussionsupporting

confidence: 72%

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

Tognon

Luppi

Corallini

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.

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Section: Discussionsupporting

confidence: 72%

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

Tognon

Luppi

Corallini

et al. 2015

Cancer

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“…If this event occurs, SV40 because of its oncogenic potential could be responsible of ependymoma and choroid plexus papilloma onset, which are pediatric brain tumors arising in children 6 months–2 years old (52, 53). It should be recalled that, in previous investigations these human cancers, together with glioblastoma multiforme (29, 54, 55) tested SV40-positive at high prevalence (6, 38, 56). In conclusion, SV40 LT Ab revealed in sera of pregnant women suggest further that SV40, or a closely related unknown polyomavirus, infects normal subjects many decades after the administration of vaccines contaminated by SV40.…”

Section: Discussionmentioning

confidence: 95%

Serum IgG Antibodies from Pregnant Women Reacting to Mimotopes of Simian Virus 40 Large T Antigen, the Viral Oncoprotein

et al. 2017

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Simian virus 40 (SV40) large T antigen (LT) coding sequences were revealed in different human samples, whereas SV40 antibodies (Ab) were detected in human sera of cancer patients and healthy individuals, although with a lower prevalence. Previous studies carried out by the neutralization assay gave a SV40 seroprevalence, in the general population, up to 8%, although higher rates, 12%, were detected in kidney transplant children, in a group of HIV-positive patients, and in healthy females. In this study, serum samples from pregnant women, together with those from non-pregnant women, were analyzed to check the prevalence of IgG Ab reacting to SV40 LT antigens. Serum samples were collected from pregnant and non-pregnant women, with the same mean age. Women were in the range of 15–48 years old. Samples were assayed by an indirect ELISA employing specific SV40 LT mimotopes as antigens, whereas functional analysis was performed by neutralization of the viral infectivity in cell cultures. As a control, sera were analyzed for Ab against BK polyomavirus (BKPyV), which is a human polyomavirus homologous to SV40. Statistical analyses employed chi-square with Yates’ correction, and Student’s t tests. Indirect ELISAs indicated that pregnant women tested SV40 LT-positive with a prevalence of 17% (23/134), whereas non-pregnant women had a prevalence of 20% (36/180) (P > 0.05). Ab against BKPyV were detected with a prevalence of 80% in pregnant women and with a prevalence of 78% in non-pregnant women. These data indicate that SV40 infects at a low prevalence pregnant women. We may speculate that SV40, or a close human polyomavirus still undetected, could be transmitted from mother to fetus.

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“…These false‐positive PCR studies may be a result of the amplification of viral vectors or viral controls used in many laboratories or the detection of presumably DNA human sequences with a high homology to SV40 DNA. This recent observation pointed out by the Martini group26, 27 is important in the verification of SV40‐positive lymphomas. Because SV40 Tag sequences between 4476–4140 bp in N′ and 2274–2630 bp in C′ are 97% homologous to the human telomeres region of chromosome 10 and 11, and as at least 1 PYD primer and the SV40 probe (4458–4479 bp) are within that region, other complementary studies should be undertaken.…”

Section: Discussionmentioning

confidence: 78%

Lack of association of polyomavirus and herpesvirus types 6 and 7 in human lymphomas

Hernández‐Losa¹,

Fedele²,

Pozo³

et al. 2005

Cancer

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BACKGROUND The association of viruses with several human tumors has been studied for almost 100 years, and it remains a very controversial issue. Due to the fact that the presence of polyomaviruses and herpes viruses reportedly are associated with lymphomas, albeit with striking results and differences between the many studies, the authors undertook a study into the presence of viral sequences of polyomavirus (BK virus, JC virus, and especially simian virus 40 [SV40]) in human lymphomas in an attempt to explain this contradictory association. To complete the study, the presence of different virus types from the herpesviriridae family were analyzed, such as herpesvirus type 6 (HHV6), HHV7, HHV8, and Epstein–Barr virus, in human lymphomas. METHODS DNA was isolated from 83 frozen human lymphoma samples, and different polymerase chain reaction techniques were used to find polyomavirus and herpesvirus sequences in these samples. To assess the incidence of the presence of sequences in lymphomas, a parallel analysis was made of 53 samples from normal donor spleen lymphocytes. Positive samples were analyzed for polyomavirus sequences by immunohistochemistry. RESULTS Polyomavirus sequences were detected in 9 of 83 lymphomas (11%), and SV40 sequences could be confirmed in only 1 lymphoma. Immunohistochemistry for large‐T antigen was negative in all samples. Herpesviruses were detected in 53 of 83 lymphomas (63.9%), were detected more frequently in Hodgkin lymphomas (80%) than in non‐Hodgkin lymphomas (58.7%), and were detected in > 60% of normal spleen lymphocytes. CONCLUSIONS The current results did not support a clear association of polyomavirus and HHV6 or HHV7 with lymphomas; HHV6 and HHV7 sequences were detected in a similar percentage of normal samples and lymphomas. The lack of significant differences between normal and malignant lymphocytes and the absence of viral protein expression in the tumor cells did not allow the establishment of a clinical correlation between polyomaviruses or HHVs (HHV6, HHV7, HHV8) and lymphomas. Nevertheless, because viral products can be lost during tumor progression, and because host factors can modulate the oncogenic role of some viruses, the hypothetical role of these viruses cannot be discarded completely. Cancer 2005. © 2004 American Cancer Society.

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Different simian virus 40 genomic regions and sequences homologous with SV40 large T antigen in DNA of human brain and bone tumors and of leukocytes from blood donors

Cited by 64 publications

References 52 publications

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

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

Serum IgG Antibodies from Pregnant Women Reacting to Mimotopes of Simian Virus 40 Large T Antigen, the Viral Oncoprotein

Lack of association of polyomavirus and herpesvirus types 6 and 7 in human lymphomas

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