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

Elisa Mazzoni,Mauro G Tognon,Marco Manfrini,Fernanda Martini,John Charles Rotondo,Mariantonietta Di Stefano,Gennaro Scutiero,Maria V Casali,Fortunato Vesce,Josè R Fiore,Federica Destro,Pantaleo Greco

doi:10.3389/fimmu.2017.00411

Elisa Mazzoni, Mauro G Tognon + Show 10 more

Open Access

https://doi.org/10.3389/fimmu.2017.00411

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Abstract

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.

Highlights

Simian virus 40 (SV40) was detected in early poliovirus vaccines
We report new data from the investigation, which determines the prevalence of Ab against SV40 large T antigen (LT), the viral oncoprotein, in pregnant women using a novel indirect ELISA with two synthetic peptides corresponding to SV40 LT mimotopes
SV40 infection has been studied in healthy individuals of different age, such as children, adults and elderly [20, 32,33,34,35,36,37] and in patients with different cancers found to be linked to SV40 [38,39,40,41,42,43]

Summary

Introduction

Simian virus 40 (SV40) was detected in early poliovirus vaccines. SV40 was present as a natural infectious agent in kidney cells, from wild macaques, employed for the production of anti-polio vaccines. Millions of individuals between 1955 and 1963 were vaccinated with anti-polio vaccines with SV40 as contaminant. These vaccines, as well as other SV40-contaminated vaccines against hepatitis A virus, respiratory syncytial virus, and adenovirus, were sources of SV40 exposure for SV40 Tag Ab in Pregnant Women the human population worldwide [1, 2]. SV40 transforms in vitro cells of different types, including human cells, whereas in vivo it induces multiple tumors in experimental animals [1, 3, 4]. SV40 sequences were revealed by molecular biology techniques, in human cancers of distinct histotypes, such as brain and bone tumors, mesothelioma, different lymphoproliferative disorders, including non-Hodgkin lymphoma. It should be recalled that these human tumors correspond to the neoplasms that are induced by SV40 in experimentally inoculated rodents [11] or in transgenic mice with SV40 Tag under tissue-specific promoter– enhancer [12, 13]

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