CORRESPONDENCE

RESPONSE: More About: Lack of Serologic Evidence for Prevalent Simian Virus 40 Infection in Humans

Denise A. Galloway, Joseph J. Carter

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 appreciate the interest and comments of Drs. O’Neill and Greenlee in regard to our recently published article (1). They suggest that simian virus 40 (SV40) DNA, or chimeric SV40/BKV genomes, are able to be pseudotyped by other polyomavirus capsids. The potential for SV40 DNA to be pseudotyped by the structural proteins of human polyomaviruses was mentioned in the "Discussion" section of our article as a possible explanation for the discrepancy between the reports that found SV40 DNA in tumors and the lack of SV40 antibodies in humans. Drs. O’Neill and Greenlee point out that it is possible to engineer chimeric viruses containing sequences of SV40 and BKV that are competent to replicate in human cells (2,3). However, the major question is, Does this phenomenon occur in vivo in humans? To our knowledge, there have been no reports in which the SV40 DNA found in tumors was shown to have a chimeric genome containing the structural genes for BKV or JCV. In fact, some reports (4) have found that the SV40 genome encodes wild-type SV40 VP1 genes. In addition, it is hard to envision conditions in vivo, including co-infection of the same cell, that would lead to recombination between SV40 and BKV or JCV. Although this theory remains a formal possibility, there is no evidence to date that recombination between SV40 and BKV or JCV occurs. Drs. O’Neill and Greenlee also cite unpublished data indicating that, in co-infections with BKV and SV40, BKV can provide a helper function to maintain the SV40 genome. It will be interesting to find out whether the persistence of SV40 DNA under these conditions is actually packaged into BKV or JCV capsids that are infectious and transmissible.

If pseudotyping of SV40 DNA were to occur, then one would predict that case patients who have tumors associated with the presence of SV40 DNA would have an increase in the prevalence of antibodies to either BKV or JCV compared with matched control subjects. Although published studies have not adequately addressed this question, our preliminary data did not indicate that there was an increase in the prevalence of BKV or JCV antibodies among case patients. A large study testing for antibodies to SV40, BKV, and JCV among case patients with non-Hodgkin’s lymphoma, which is a cancer type that others (5,6) have shown to be associated with SV40, and control subjects will definitively determine whether there is an increased prevalence of antibodies to any of these polyomaviruses among case patients.

Overall, we do not consider pseudotyping of SV40 DNA by polyomavirus capsids as the most likely explanation for the observation that SV40 virus-specific antibodies were not detected in humans. The fact that our study (1) and another study (7) have found a low level of antibodies that cross-reacted with SV40 and BKV or JCV, suggests that the presence of SV40-reactive antibodies is not likely to be due to infection with SV40 but rather to infection with other human polyomaviruses. It will be crucial to identify either chimeric polyomavirus genomes or BKV/JCV-pseudotyped SV40 genomes to lend support to the hypothesis proposed by Drs. O’Neill and Greenlee.

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 O’Neill FJ, Xu X, Gao Y. Host range analysis of a chimeric simian virus 40 genome containing the BKV capsid genes. Virus Res 1992;25:169–87.[CrossRef][ISI][Medline]

3 O’Neill FJ, Miller TH, Stevens R. Complementation between SV40 and RFV defectives and acquisition of SV40 origins by late RFV genomes. Virology 1986;154:344–56.[ISI][Medline]

4 Stewart AR, Lednicky JA, Butel JS. Sequence analyses of human tumor-associated SV40 DNAs and SV40 viral isolates from monkeys and humans. J Neurovirol 1998;4:182–93.[ISI][Medline]

5 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]

6 Shivapurkar N, Harada K, Reddy J, Scheuermann RH, Xu Y, McKenna RW, et al. Presence of simian virus 40 DNA sequences in human lymphomas. Lancet 2002;359:851–2.[CrossRef][ISI][Medline]

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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