Serological Cross-Reactivities between Antibodies to Simian Virus 40, BK Virus, and JC Virus Assessed by Virus-Like-Particle-Based Enzyme Immunoassays

Abstract

Enzyme immunoassays (EIAs) for detection of serum antibodies to simian virus 40 (SV40), BK virus (BKV), and JC virus (JCV) were developed by using virus-like-particles (VLPs) produced in insect cells from recombinant baculoviruses expressing the VP1 protein of the respective virus. Rhesus macaque sera with neutralizing antibodies to SV40 showed a high level of reactivity in the SV40 VLP-based EIA, and these sera also showed lower levels of reactivity in the BKV and JCV VLP-based EIAs. Rhesus macaque sera negative for neutralizing antibodies to SV40 were negative in all three EIAs. Competitive binding assays showed that SV40 VLPs inhibited BKV reactivity. In rhesus macaque sera, high optical density (OD) values for antibodies to SV40 VLPs were correlated with high OD values for antibodies to BKV but not with high OD values for antibodies to JCV VLPs. Human sera with neutralizing antibodies to SV40 were more reactive to SV40 VLPs than human sera without neutralizing antibodies to SV40. The greater SV40 reactivities of human sera were correlated with greater reactivities to BKV VLPs but not JCV VLPs. These data suggest that cross-reactivity with BKV antibodies may account for part of the low-level SV40 reactivity seen in human sera. With their greater versatility and their suitability for large-scale testing, the VLP-based EIAs for SV40, BKV, and JCV are likely to contribute to a better understanding of the biology of these viruses.

High prevalence of serum antibodies reacting with simian virus 40 capsid protein mimotopes in patients affected by malignant pleural mesothelioma

“…Data obtained in normal individuals suggest that natural SV40 infection occurs in human populations with a prevalence lower than that of the ubiquitous JCV and BKV (60-90%) (25). It is possible that SV40 is transmitted through contact in the human environment.…”

“…Contrasting reports have appeared in the literature on the presence of SV40 footprints in humans and its association with human tumors (20)(21)(22). SV40 antibody detection had been attempted in several studies using serologic methods with SV40 virus-like particles (VLPs), but because of high protein homology among the three main polyomaviruses SV40, BKV, and JCV, the results were always affected by some cross-reactivity (23)(24)(25)(26)(27)(28)(29)(30).…”

Absence of SV40 antibodies or DNA fragments in prediagnostic mesothelioma serum samples

“…Recently published studies have shown that SV40 reactivity in human sera may be almost entirely a result of cross-reactivity with BKV and JCV antibodies. 24,25,46 Also in the present study, when SV40 VP1 antibodies were measured in the antibody capture assay without precautions to suppress crossreactive BKV and JCV VP1 antibodies they were correlated with BKV and/or JCV VP1 responses.…”

“…This may imply that the frequent finding of SV40 DNA fragments in mesothelioma tumors either is caused by enhanced viral replication favored by the disease process, 47 or that it simply stems from contamination. 10,11 The study was designed on the assumption that SV40 in humans induces persistent infections with a continuous and relatively high production of antibodies as it does in monkeys 24 and similar to the serum responses seen with BKV and JCV infections in humans. Antibodies to VP1 are then expected to be a marker of acute or persistent infection.…”

“…23 Infection with human polyomaviruses BK (BKV) and JC (JCV), which are closely related to SV40, is frequent and leads to strong antibody responses that can cross-react with SV40 antigens. 24 After performing competitive inhibition experiments using BKV and JCV, the prevalence of seropositivity in zoo workers was reduced to 10%. 23 Results of old and recent studies are thus difficult to compare because of use of different assay principles and varying sensitivities.…”