TY - JOUR T1 - Antibodies reacting to mimotopes of Simian virus 40 large T antigen, the viral oncoprotein, in sera from children. JF - J Cell Physiol Y1 - 2019 A1 - Mazzoni, Elisa A1 - Frontini, Francesca A1 - Rotondo, John Charles A1 - Zanotta, Nunzia A1 - Fioravanti, Arianna A1 - Minelli, Francesca A1 - Torreggiani, Elena A1 - Campisciano, Giuseppina A1 - Marcuzzi, Annalisa A1 - Guerra, Giovanni A1 - Tommasini, Alberto A1 - Touzé, Antoine A1 - Martini, Fernanda A1 - Tognon, Mauro A1 - Comar, Manola AB -

Recent data indicate that the Simian virus 40 (SV40) infection appears to be transmitted in humans independently from early SV40-contaminated antipolio vaccines. Serum antibodies against SV40 large T antigen (Tag) were analyzed in children/adolescents and young adults. To investigate antibodies reacting to SV40 Tag antigens, serum samples ( n = 812) from children and young adults were analyzed by indirect ELISAs using specific SV40 Tag mimotopes. Mimotopes were synthetic peptides corresponding to SV40 Tag epitopes. In sera ( n = 412) from healthy children up to 17 years old, IgG antibodies against SV40 Tag mimotopes reached an overall prevalence of 15%. IgM antibodies against SV40 Tag were detected in sera of children 6-8 months old confirming and extending the knowledge that SV40 seroconversion occurs early in life. In children/adolescents affected by different diseases ( n = 180) SV40 Tag had a prevalence of 18%, being the difference no significant compared to healthy subjects ( n = 220; 16%) of the same age. Our immunological data indicate that SV40 circulates in children and young adults, both in healthy conditions and affected by distinct diseases. The IgM detection in sera from healthy children suggests that the SV40 infection/seroconversion occurs early in life (>6 months). Our immunological data support the hypothesis that SV40, or a closely related still unknown polyomavirus, infects humans. The SV40 seroprevalence is lower than common polyomaviruses, such as BKPyV and JCPyV, and other new human polyomaviruses. In addition, our immunological surveillance indicates a lack of association between different diseases, considered herein, and SV40.

VL - 234 IS - 4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/30362540?dopt=Abstract ER - TY - JOUR T1 - Immunologic evidence of a strong association between non-Hodgkin lymphoma and simian virus 40. JF - Cancer Y1 - 2015 A1 - Tognon, Mauro A1 - Luppi, Mario A1 - Corallini, Alfredo A1 - Taronna, Angelo A1 - Barozzi, Patrizia A1 - Rotondo, John Charles A1 - Comar, Manola A1 - Casali, Maria Vittoria A1 - Bovenzi, Massimo A1 - D'Agostino, Antonio A1 - Vinante, Fabrizio A1 - Rigo, Antonella A1 - Ferrarini, Isacco A1 - Barbanti-Brodano, Giuseppe A1 - Martini, Fernanda A1 - Mazzoni, Elisa KW - Adult KW - Aged KW - Antibodies, Viral KW - Capsid Proteins KW - Enzyme-Linked Immunosorbent Assay KW - Female KW - Humans KW - Lymphoma, Non-Hodgkin KW - Male KW - Middle Aged KW - Polyomavirus Infections KW - Seroepidemiologic Studies KW - Simian virus 40 KW - Tumor Virus Infections AB -

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 = 89] and NHL2 [n = 61]) along with controls represented by oncologic patients affected by breast cancer (BC; n = 78) and undifferentiated nasopharyngeal carcinoma (UNPC; n = 64) and 3 different cohorts of healthy subjects (HSs; HS1 [n = 130], HS2 [n = 83], and HS3 [n = 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.

CONCLUSIONS: Our data indicate a strong association between NHL and SV40 and thus a need for innovative therapeutic approaches for this hematologic malignancy.

VL - 121 IS - 15 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25877010?dopt=Abstract ER - TY - JOUR T1 - High prevalence of serum antibodies reacting with simian virus 40 capsid protein mimotopes in patients affected by malignant pleural mesothelioma. JF - Proc Natl Acad Sci U S A Y1 - 2012 A1 - Mazzoni, Elisa A1 - Corallini, Alfredo A1 - Cristaudo, Alfonso A1 - Taronna, Angelo A1 - Tassi, Gianfranco A1 - Manfrini, Marco A1 - Comar, Manola A1 - Bovenzi, Massimo A1 - Guaschino, Roberto A1 - Vaniglia, Francesca A1 - Magnani, Corrado A1 - Casali, Ferruccio A1 - Rezza, Giovanni A1 - Barbanti-Brodano, Giuseppe A1 - Martini, Fernanda A1 - Tognon, Mauro G KW - Amino Acid Sequence KW - Antibodies, Viral KW - Capsid Proteins KW - Enzyme-Linked Immunosorbent Assay KW - Female KW - Humans KW - Male KW - Mesothelioma KW - Molecular Sequence Data KW - Pleural Neoplasms KW - Pregnancy KW - Simian virus 40 AB -

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.

VL - 109 IS - 44 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23071320?dopt=Abstract ER - TY - JOUR T1 - Simian virus 40 efficiently infects human T lymphocytes and extends their lifespan. JF - Exp Hematol Y1 - 2012 A1 - Mazzoni, Elisa A1 - Rigolin, Gian Matteo A1 - Alaribe, Franca Nneka A1 - Pancaldi, Cecilia A1 - Maniero, Stefania A1 - Comar, Manola A1 - Martini, Fernanda A1 - Tognon, Mauro KW - Antigens, Polyomavirus Transforming KW - Cell Line, Transformed KW - Cell Survival KW - Humans KW - Microscopy, Electron, Transmission KW - Simian virus 40 KW - T-Lymphocytes AB -

The relevance of viral infections to the onset and progression of human hematologic malignancies and other blood diseases is still a matter of active investigation. Purified human T lymphocytes isolated from the peripheral blood mononuclear cells of healthy blood donors were experimentally infected with simian virus 40 (SV40), a small DNA tumor virus. SV40-positive T lymphocytes extended their lifespan up to day 80 postinfection (PI). Expression of viral antigens, such as the large T antigen and the viral capsid protein VP1 from the early and late regions, respectively, was detected up to day 40 PI. SV40 viral progeny were continuously produced from day 10 to 40 PI. SV40 DNA sequences were detected in infected T cells for up to 80 days. Our data indicate that human T lymphocytes can be efficiently infected with SV40. Although T cells infected by SV40 were not immortalized, 30% of these lymphocytes appeared to be morphologically transformed with an enlarged T-cell shape. Our investigation provides a simple model for studying the interactions of human T lymphocytes with this small DNA tumor virus and it might represent an experimental tool for investigating new biomarkers and targets for innovative therapeutic approaches.

VL - 40 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/22421183?dopt=Abstract ER - TY - JOUR T1 - Merkel cell polyomavirus DNA sequences in the buffy coats of healthy blood donors. JF - Blood Y1 - 2011 A1 - Pancaldi, Cecilia A1 - Corazzari, Valentina A1 - Maniero, Stefania A1 - Mazzoni, Elisa A1 - Comar, Manola A1 - Martini, Fernanda A1 - Tognon, Mauro KW - Adult KW - Aged KW - Base Sequence KW - Blood Buffy Coat KW - Carcinoma, Merkel Cell KW - Databases, Nucleic Acid KW - DNA, Viral KW - Expressed Sequence Tags KW - Humans KW - Italy KW - Middle Aged KW - Molecular Sequence Data KW - Polymerase Chain Reaction KW - Polyomavirus KW - Polyomavirus Infections KW - Prevalence KW - Reverse Transcriptase Polymerase Chain Reaction KW - Sequence Alignment KW - Sequence Analysis, DNA KW - Tumor Virus Infections KW - Viral Load KW - Young Adult AB -

Merkel cell polyomavirus (MCPyV), a DNA tumor virus, has been found to be associated with Merkel cell carcinoma and chronic lymphocytic leukemia. MCPyV sequences have also been detected in various normal tissues in tumor-affected patients. Immunologic studies have detected MCPyV antibodies in as many as 80% of healthy blood donors. This high seroprevalence suggests that MCPyV infection is widespread in humans. In our study, buffy coats, which were examined for MCPyV DNA Tag sequences, showed a prevalence of 22%. Viral DNA load was revealed in blood samples from 10 to 100 molecules/100 000 cells. DNA sequencing confirmed that polymerase chain reaction amplicons belong to the MCPyV strain, MKL-1. To interpret the putative role of MCPyV in chronic lymphocytic leukemia, we may infer that, during a long period of viral persistence in blood cells, this DNA tumor virus may generate mutants, which are able to participate as cofactors in the multistep process of cell transformation.

VL - 117 IS - 26 U1 - http://www.ncbi.nlm.nih.gov/pubmed/21464370?dopt=Abstract ER -