CORRESPONDENCE

Re: Lack of Serologic Evidence for Prevalent Simian Virus 40 Infection in Humans

Regis A. Vilchez, Janet S. Butel

Affiliations of authors: Departments of Medicine and of Molecular Virology and Microbiology (RAV), and Department of Molecular Virology and Microbiology (JSB), Baylor College of Medicine, Houston, TX

Correspondence to: Regis A. Vilchez, MD, Department of Medicine, Section of Infectious Diseases, One Baylor Plaza, BCM-286, Rm. N1319, Houston, TX 77030 (e-mail: rvilchez{at}bcm.tmc.edu)

We read with interest the article by Carter et al. (1) in which the authors performed a retrospective cross-sectional study using an enzyme-linked immunosorbent assay (ELISA) to determine the presence of simian virus 40 (SV40) antibodies in serum samples from three patient groups and from macaques. The results of their study indicated that the frequency of SV40 antibodies in human samples was 6.6%, that the ELISA detected cross-reactive antibodies for JCV, BKV (common human polyomaviruses), and SV40 in both human and macaque sera, and that the prevalence of authentic SV40 antibodies in human sera was unclear. These findings are similar to those of another retrospective analysis using enzyme immunoassays (2) in which serum samples from humans and macaques showed cross-reactivity to all three polyomaviruses. These demonstrations of cross-reactive antibodies are not surprising because ELISAs can detect non-neutralizing antibodies, and the assays used in the above-mentioned studies were based on the polyomavirus major capsid protein VP1, which shares some epitopes among the three viruses (3).

The dynamics of SV40 infections in humans and the immune response to those infections are not fully characterized. Some issues to consider in this regard are that human responses to SV40 may not be comparable to those against more common viral pathogens (e.g., adenovirus and herpesvirus) and that specific antibodies to SV40 may wane without re-infection. Interestingly, children receiving a known SV40-contaminated oral poliovirus vaccine were shown to excrete infectious SV40 in their stools for up to 5 weeks after vaccination but none showed a neutralizing antibody response to the viral infection (4).

It is agreed among those in the research community that prospective studies using sensitive and specific reagents for SV40 are needed to determine the prevalence of viral infections in the general population and to define groups of individuals at elevated risk for SV40-linked disease. However, for the reasons cited above, serologic tests alone may not be the most reliable way to conduct those studies (3). For example, serologic assays for identification of human infections with herpes B virus of macaques are limited by low sensitivity and specificity, similar to reports concerning SV40 assays (5). The herpes B virus system illustrates that the immune response in macaques to a given virus may not predict the human response to the same virus. Serologic assays may also be of minimal use for diagnosing or making therapeutic decisions in regard to SV40 infection because most overt polyomavirus infections presumably result from reactivation of latent infections (3). Cell culture for JCV, BKV, and SV40 infections is rarely helpful in diagnosing infection because of slow viral growth and the requirement for specialized cell lines (3). Therefore, modern molecular biology techniques, such as real-time polymerase chain reaction (PCR) and conventional PCR with sequence analysis, which are known to be highly sensitive and specific for SV40, are excellent alternatives for the analysis of SV40 infections and for studies of SV40 prevalence in humans. These techniques have been recognized as essential tools for providing insights into the possible infectious etiology of human malignancies (3).

In conclusion, future studies need to focus on how SV40 is transmitted among humans, how it is distributed throughout the infected host, and how the host responds immunologically. Indeed, the Institute of Medicine (6) recognized that those gaps in our understanding of the pathogenesis of SV40 infections in humans are important and recommended targeted biologic research of SV40 infection in humans.

REFERENCES

1 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.[Abstract/Free Full Text]

2 Viscidi RP, Rollison DE, Viscidi E, Clayman B, Rubalcaba E, Daniel R, et al. Serological cross-reactivities between antibodies to simian virus 40, BK virus and JC virus assessed by virus-like-particle-based enzyme immunoassays. Clin Diagn Lab Immunol 2003;10:278–85.[Abstract/Free Full Text]

3 Khalili K, Stoner GL. Human polyomaviruses: molecular and clinical perspectives. New York (NY): Wiley-Liss; 2001. p. 54.

4 Melnick JL, Stinebaugh S. Excretion of vacuolating SV-40 virus (papova virus group) after ingestion as a contaminant of oral poliovaccine. Proc Soc Exp Biol Med 1962;109:965–8.

5 Huff JL, Barry PA. B-virus (Cercopithecine herpesvirus 1) infection in humans and macaques: potential for zoonotic disease. Emerg Infect Dis 2003;9:246–50.[ISI][Medline]

6 Stratton K, Almario DA, McCormick MC. SV40 contamination of polio vaccine and cancer. Immunization Safety Review Committee, Board of Health Promotion and Disease Prevention, Institute of Medicine of the National Academies. Washington (DC): The National Academies Press. 2003.



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