Serological evidence of SV40 infections in HIV-infected and HIV-negative adults

Abstract

SV40 is a simian polyomavirus that was a contaminant of some viral vaccines administered to people between 1955 and 1962. SV40 DNA has recently been found associated with several types of human tumors, suggesting that the virus is present in humans. We examined sera from patients infected with human immunodeficiency virus type 1 (HIV-1) as well as from HIV-1-negative controls to determine the prevalence of SV40 neutralizing antibodies using a specific plaque reduction assay. We found that 16.1% of HIV-infected patients (n = 236) were seropositive for SV40, as compared to 12.0% of HIV-negative control volunteers (n = 108) and 11.1% of HIV-negative patients (n = 72). These differences were not statistically significant. As individuals born between 1941 and 1962 had the highest chance of having received SV40-contaminated poliovaccines, we analyzed SV40 seropositivity rates based on year of birth. SV40 antibody rates for HIV-infected patients born before 1941, between 1941 and 1962, and after 1962 were 17.1%, 16.3%, and 11.8%, respectively. For the HIV-negative subjects, the rates were 12.5%, 12.0%, and 9.7%, respectively. There was no correlation between SV40 seropositivity and either the stage of disease in HIV-infected patients or the race/ethnicity. Also, there was no correlation between the presence of SV40 neutralizing antibody and the titer of neutralizing antibody to human polyomavirus BKV. The SV40 seropositivity rates in the patients born between 1941 and 1962 may be explained by the likelihood of those individuals having received SV40-contaminated vaccines, but the detection of SV40 neutralizing antibody in individuals born after 1962 (with no risk of having received contaminated vaccines) is significant. Although cross-reactive antibodies might theoretically contribute to the observed reactivities, these results suggest that SV40 neutralizing antibodies are present in certain individuals and raise the possibility that SV40 continues to infect humans long after vaccines were freed from contamination.

Investigation of the simian polyomavirus SV40 as a potential causative agent of human neurological disorders in AIDS patients

“…SV40 was introduced on a large scale into the human population during the years 1955±1963 through polio vaccines contaminated by this viral agent [42]. Many investigations con®rm that SV40, although primarily a monkey virus, can infect man [9,10,17,19,31]. Patient 41 was too young to have received an SV40-contaminated polio vaccine.…”

“…SV40 isolates from PML have been questioned recently [29,30] but the ability of SV40 to infect man is well documented [9,10,20,23]. SV40 DNA sequences have been detected by PCR in normal tissues [9,10,17,19], and SV40-neutralising antibodies have been detected in both HIV-negative (11%) and HIV-positive (16%) individuals [31].…”

Different simian virus 40 genomic regions and sequences homologous with SV40 large T antigen in DNA of human brain and bone tumors and of leukocytes from blood donors

“…3 SV40 DNA was detected in PBMCs and brain tissue of monkeys, 21 and SV40 neutralizing antibodies were found in human sera. 22 In most studies, SV40 sequences were detected by PCR amplification, suggesting that SV40 infection in human tumors and normal tissues commonly results in a low viral load. Indeed, by using a semiquantitative PCR assay we determined 10 Ϫ2 to 10 Ϫ4 SV40 genome equivalents per cell in DNA samples from human lymphoproliferative disorders and from PBMCs of blood donors.…”

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

“…Several studies of recently collected sera from age groups probably vaccinated with SV40-contaminated preparations also have not found high-titre SV40. 21,25,46,[49][50][51] It should be noted, however, that all comparisons with previous serological results might be dubious because of the difficulties encountered with cross-reactivity of antibodies.…”

“…In groups assumed to have been exposed to contaminated vaccine 12-24% were seropositive for neutralizing antibodies, while in groups born after vaccines were SV40-free seropositivity rates of 2-13% were seen. [19][20][21] Among laboratory workers handling monkeys or monkey kidney cells 40-55% have been found to be positive for SV40 neutralizing antibodies, 20,22 and in zoo workers with direct contact with nonhuman primates 25% had a positive response when an enzyme immunoassay was used. 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.…”