Antibodies reacting to mimotopes of Simian virus 40 large T antigen, the viral oncoprotein, in sera from children

Abstract

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.

Association Between Simian Virus 40 and Human Tumors

“…Indeed, SV40 DNA sequences were detected in normal tissues, such as PBMCs (161, 182, 187), leukocytes from organ and blood donors (180, 181), and pituitary tissues (179). Specific immunological assays identified IgG and IgM antibodies against SV40 VPs and Tag in sera from normal children, adults and elderly subjects (190, 191, 193, 194). In addition, SV40 neutralizing antibodies were detected, in different investigations, using the plaque reduction assay, which is a high specific test demonstrating that the SV40 infection occurred in subjects/patients (203, 210, 285).…”

“…SV40 primary infection occurs early in life and its seroprevalence increases with age. Anti-SV40 antibodies in the serum of immunized individuals and SV40 antigens have been detected in normal subjects (190–199). Lusting et al reported a prevalence of serum anti SV40 antibodies in 7.6–14% of Swedish children aged from 1 to 13 years old (198).…”

“…Immunological data showed that healthy blood donors carry IgG antibodies reacting to SV40 VPs and Tag with a prevalence of 18 and 20%, respectively (191, 192). Furthermore, immunological data from children may suggest that SV40 infection/seroconversion occurs early in life, i.e., at 6 months of age (190, 193).…”

“…It is plausible that this PyV may act as a co-factor during the tumorigenic process, either during the early phase of oncogenesis or in the late phase of tumor progression. Indeed, as for other viruses (17), in normal physiological conditions, the immune system counteracts the oncogenic potential of SV40 (194) whose infection could be acquired early in life (190, 193). However, in certain host conditions, such as in immunocompromised individuals, SV40 may exert its oncogenic activities.…”

Immunological evidence of an early seroconversion to oncogenic Merkel cell polyomavirus in healthy children and young adults

“…Sera (n = 344) were from HC aged 0-20 years old (mean age AE standard deviation of mean [SD], 9 AE 7 years old), with unknown MCPyV serology. HC sera were from our archive [44], and collected, as reported [22]. Samples were collected at the Clinical Laboratory Analysis, University Hospital of Ferrara (years 2016-2018).…”