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

Extract

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 O’Neill and Greenlee also cite unpublished data indicating that, in co-infections with BKV and SV40, BKV can provide a helper function to maintain the SV40 genome.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.