© 2004 by Oxford University Press
© 2004 Oxford University Press
CORRESPONDENCE |
RESPONSE: Re: Lack of Serologic Evidence for Prevalent Simian Virus 40 Infection in Humans
Affiliation of authors: Fred Hutchinson Cancer Research Center, Seattle, WA
Correspondence to: Denise A. Galloway, PhD, Fred Hutchinson Cancer Center, 1100 Fairview Ave. N, Rm. C1-105, P.O. Box 19024, Seattle, WA 98109-1024 (e-mail: dgallowa{at}fhcrc.org)
We agree with Vilchez and Butel’s comments that serology is but one of several valid methods for examining the question of whether simian virus 40 (SV40) is circulating in the general population. The utility of polymerase chain reaction (PCR)-based methods for detecting SV40 DNA is indisputable; however, PCR results may be compromised by problems with specificity and/or contamination with plasmids containing SV40 sequences. Inter-laboratory comparisons of PCR methods have been equivocal (1). In addition, it will be important to determine the copy number of SV40 sequences in tumor tissues to determine whether SV40 sequences are present in every cell of the tumor. Serology must address similar issues of sensitivity and specificity, and we are currently validating our methods by comparing them with those of another laboratory using blinded samples.
Vilchez and Butel point out that the dynamics of the SV40 antibody response in humans is not known. However, it is known that the human antibody response to other polyomaviruses and the macaque antibody response to infection by SV40 are vigorous and long-lasting. In our study (2), no human serum was found to have a vigorous antibody response specific for SV40 infection, whereas macaque sera had a pronounced response to SV40 infection. This finding suggested that SV40 antibody responses in humans were either extremely rare or, unlike other polyomavirus infections, of very low titer. Children who received oral SV40-contaminated poliovirus vaccine did not produce high-titer SV40 antibody responses; however, individuals who were injected with SV40-contaminated vaccines did have high-titer SV40 antibody responses (3). Together these findings suggest that, although SV40 is immunogenic, it is likely that there is not a sufficient quantity of virus to engender an antibody response when administered to humans in the oral form. Studies that have detected SV40 DNA in tumors in individuals who were not exposed to SV40-contaminated poliovirus vaccines would suggest that SV40 infection is widespread in the population (4). However, it is difficult to understand how SV40 could produce enough virus to be effectively transmitted without generating an antibody response in infected individuals.
Our results are consistent with several recent epidemiologic studies (5,6) that have failed to detect an association between exposure to SV40-contaminated poliovirus vaccines and human cancers and with the Viscidi laboratory (7), where no association between SV40 seropositivity and lymphoma was found. Although it is impossible to prove the absence of any SV40 infection in the population, the consistency of these findings, using different populations and methods, provides compelling evidence to suggest that SV40 is not a prevalent human pathogen.
REFERENCES
1 Strickler HD; International SV40 Working Group. A multicenter evaluation of assays for detection of SV40 DNA and results in masked mesothelioma specimens. Cancer Epidemiol Biomarkers Prev 2001;10:523–32.
2 Carter JJ, Madeleine MM, Wipf GC, Garcea RL, Pipkin PA, Minor PD, et al. Lack of serologic evidence for prevalent simian virus 40 infection in humans. J Natl Cancer Inst 2003;95:1522–30.
3 Shah KV. Does SV40 infection contribute to the development of human cancers? Rev Med Virol 2000;10:31–43.[CrossRef][Medline]
4 Vilchez RA, Madden CR, Kozinetz CA, Halvorson SJ, White ZS, Jorgensen JL, et al. Association between simian virus 40 and non-Hodgkin lymphoma. Lancet 2002;359: 817–23.[CrossRef][ISI][Medline]
5 Engels EA, Rodman LH, Frisch M, Goedert JJ, Biggar RJ. Childhood exposure to simian virus 40-contaminated poliovirus vaccine and risk of AIDS-associated non-Hodgkin’s lymphoma. Int J Cancer 2003;106:283–7.[CrossRef][ISI][Medline]
6 Strickler HD, Goedert JJ, Devesa SS, Lahey J, Fraumeni JF Jr, Rosenberg PS. Trends in U.S. pleural mesothelioma incidence rates following simian virus 40 contamination of early poliovirus vaccines. J Natl Cancer Inst 2003;95:38–45.
7 de Sanjose S, Shah KV, Domingo-Domenech E, Engels EA, Fernandez de Sevilla A, Alvaro T, et al. Lack of serological evidence for an association between simian virus 40 and lymphoma [published erratum appears in Int J Cancer 2003;104:800]. Int J Cancer 2003;104:522–4.[CrossRef][ISI][Medline]
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