The significance of those infections to the health of the affected individuals is unknown

The significance of those infections to the health of the affected individuals is unknown. Funding Statement This work was supported in part by research grant R01 CA104818 (JSB) from the National Institutes of Health, United States of America, the University of Trieste (MC), and the University of Ferrara (MT), Italy. Samples were assayed by two different serological methods, one group by neutralization of viral infectivity and the other by indirect ELISA employing specific SV40 mimotopes as antigens. Viral DNA assays by real-time polymerase chain reaction were carried out on blood samples. Results Neutralization and ELISA assessments indicated that this pregnant women were SV40 antibody-positive with overall prevalences of 10.6% (13/123) and 12.7% (14/110), respectively. SV40 neutralizing antibodies were detected in a low number of cord blood samples. Antibody titers were generally low. No viral DNA was detected in either maternal or cord bloods. Conclusions SV40-specific serum antibodies were detected in pregnant women at the time of delivery and in cord bloods. There was no evidence of transplacental transmission of SV40. These data indicate that SV40 is circulating at a low prevalence in the northern Italian population long after the use of contaminated vaccines. Introduction Simian virus 40 (SV40), a monkey polyomavirus, was discovered in 1960 as a contaminant of poliovirus vaccines which had been produced in naturally infected macaque kidney cells [1]. SV40-contaminated vaccines were inadvertently administered to millions of recipients between 1955 and 1963, providing a documented source of human exposure to SV40 [2]C[4]. The virus is widely recognized as having potent cell transforming ability and oncogenic activity in experimental animals [4]C[7]. This activity raised a concern that SV40 might cause human infections and perhaps contribute to cancer development. SV40 DNA sequences have been detected GW3965 HCl in blood, urine, and tissue samples from healthy individuals [8]C[23]. SV40 DNA also has been found in association with several types of human cancer, including brain tumors, mesotheliomas, osteosarcomas, and lymphomas [8], [10], [11], [13], [24]C[39]. However, the International Agency for Research on Cancer decided recently that there was not enough firm evidence to classify SV40 as a carcinogenic viral agent of humans [40]. Although there is strong evidence that infections have occurred in certain populations in different geographic regions, more studies are needed of the current prevalence of SV40 infections in humans and the natural history of those infections [3], [4], [39], [41], [42]. Seroprevalence surveys are a common approach to examining the distribution of a virus within a host population. Neutralization assays, the most highly specific method for detection of viral antibodies in human sera, have been used in many studies [4], [9], [43]C[48]. SV40 seroprevalences generally have been in the range of 5C8%, although higher rates were detected in GW3965 HCl children who had received kidney transplants, in a group of HIV-positive men, and in Hispanic women in Texas (USA) [9], [44], [48]. However, this methodology is time consuming, labor intensive, lengthy, expensive, and requires specialized skills. Because of these limitations, neutralization assays are not practical for large epidemiological studies. Detection of SV40 antibodies has been attempted using enzyme immunoassays and SV40 virus-like particles or soluble capsid proteins. In those assays, all binding antibodies are measured, including non-neutralizing ones and those that recognize cross-reacting antigens on BK virus (BKV) and JC virus (JCV), resulting in some non-specificity concerns [49]C[51]. A newly GW3965 HCl developed ELISA employing specific SV40 synthetic peptides mimicking epitopes of viral capsid proteins VP1C3 seems to circumvent those problems [52]C[57]. Recent studies with this new assay have documented SV40 antibodies in Italian populations with estimated seroprevalences of 10C18%. Higher prevalences have been observed among patients with mesotheliomas and glioblastomas [53], [57]. Both DNA-based studies and serological surveys have detected SV40 markers in individuals too young to have been exposed to SV40-contaminated vaccines. These observations suggest that SV40 is being horizontally transmitted in humans. Maternal-infant transmission has been hypothesized to be a possible route of transmission of polyomaviruses [58]. This has been shown to occur in animal models, but no data substantiate that mode of transmission in humans [59]C[64]. This study was designed to determine the prevalence of SV40 antibodies in pregnant women and in their GW3965 HCl newborns and to examine the possibility of transplacental transmission of the virus. Materials and Methods Samples Serum samples were collected at the time of delivery from a total of 233 healthy AXUD1 pregnant women and 100 matched cord blood samples from newborns. The enrolled women and their offspring were all of Caucasian origin and all the women were in their first pregnancy. Maternal serum collections represented two cohorts (Cohort A, n?=?123, and Cohort B, n?=?110), from Trieste and Ferrara, Italy, respectively. Cord blood samples [Cohort A(cb), n?=?100] were collected at time of delivery of mothers in Cohort A. The demographics of study participants are shown in Table 1. The first group of maternal serum samples (Cohort A, n?=?123) and a portion of the cord blood samples (n?=?13) were analyzed for SV40 neutralizing antibodies in the Department of Molecular Virology and Microbiology, Baylor College GW3965 HCl of Medicine, Houston, Texas, USA, using a plaque-reduction.