We found that, overall, SV40 DNA sequences are rarely present in lymphomas from both immunocompetent and immunodeficient patients, and we further confirmed the presence of SV40 in most human mesotheliomas. Thus, SV40 does not appear to be related to the increased incidence of lymphomas observed in the second half of this century, but may be related to mesothelioma devel-opment. Some of the lymphomas tested positive for SV40 only when we used the very sensitive SV5/SV6 primers for the RB-pocket binding domain of Tag, and negative when tested with primers for the SV40 regulatory region. This suggests that, in these samples, only a few cells were SV40 positive. SV40 sequences have been detected in peripheral blood lymphocytes and granulocytes from normal individuals. Furthermore, it has been suggested that circulating mononuclear phagocytes may represent a reservoir for SV40 in humans. other
Thus, it is possible that the positive results obtained for tumors with the very sensitive SV5/SV6 set of primers are related to the presence of SV40-positive mononuclear phagocytes within the tumor tissue, rather than representing tumor-associated virus. If this hypothesis is correct, all of the non-Hodgkin’s lymphomas that developed in the nonimmunocompromised group we tested should be considered SV40 negative. The rare association of SV40 with human lymphomas and leukemias is supported by a recent study in which SV40 was found in only 6 of 15 B-cell immuno-blastic lymphomas, and SV40 was not detected in 20 myeloid leukemias and 9 large cell lymphomas (Carl W. Miller, PhD; personal communication; May 1998). However, it has also been suggested that SV40 could be present in lymphoma cells in the early phase of lymphomagenesis to promote transformation, remaining present afterwards only in a fraction of the tumor cells and eventually in none of the tumor cells during tumor progression. In support of this hypothesis, Salewski et al demonstrated very recently that SV40 is required to induce the transformed phenotype but it is not required for the maintenance of the transformed phenotype. Actually, following SV40-mediated transformation, cells that lost SV40 became more aggressive and oncogenic, possibly because the immune system did not react against the SV40 tumor antigens that are highly immunogenic. It is unknown how frequently SV40 transformed cells lose SV40, but it is possible that the number of SV40-positive tumors could be underestimated when advanced malignancies are tested.