Polyomaviruses in solid-organ transplant recipients.

Abstract

We have recently read with interest a review written by Mylonakis et al. (1). In their overview, the authors commented that BK virus (BKV) and JC virus (JCV) cause interstitial nephritis in 5% of renal transplant recipients and that up to 45% of the affected patients may develop allograft failure. Also, the authors described polymerase chain reaction assay and other molecular biology studies, which were derived from polyomavirus simian virus 40 (SV40), that serve as useful adjunctive diagnostic tools. However, the homology between the two human polyomaviruses (JCV and BKV) and SV40 is approximately 70%; thus, confirmatory tests are necessary to identify with certainty polymerase chain reaction amplicons. Other studies have used anti-SV40 immunohistochemical reagents and assumed that BKV was detected by cross-reactivity. These points are important because recent reports have indicated that SV40 can cause infections in kidney transplant recipients. It is possible that some BKV detections have actually been caused by the presence of SV40. The history of polyomavirus SV40 and its pathogenesis in humans begins with the polio vaccine. Both inactivated and live attenuated forms of the polio vaccine were prepared using primary rhesus monkey kidney cells, some of which were from animals naturally infected with SV40, a virus that was not known at the time (2). Residual infectious SV40 survived the vaccine inactivation treatments, and millions of people were inadvertently exposed to live SV40 from 1955 through early 1963 when SV40-contaminated vaccines were administered (2). However, it is not known which individuals received contaminated vaccines or the amount of live SV40 in particular vaccine lots. Seroepidemiology studies (3,4,5) in adults and children have shown the presence of SV40-neutralizing antibodies in individuals exposed to contaminated vaccines and in individuals born after 1963. However, few published studies have examined SV40 antibodies in renal transplant recipients. An early report by Shah et al. (5) found 3 of 17 adult kidney transplant patients to have neutralizing antibodies to SV40. More recently, it was demonstrated that SV40 seropositivity in children increased with age (P =0.01) and was significantly associated with kidney transplantation (P =0.001) (4). In addition, serum samples from selected children were tested for BKV-neutralizing antibodies, and no correlation was found between the presence of antibody to SV40 and the level of anti-BKV titers. These observations suggest that polyomavirus SV40 is causing infections in humans long after the use of the contaminated vaccines. More importantly, SV40 DNA was identified in four renal transplant patients (6). The viral sequences detected among the kidney transplant recipients showed greater genetic variation than those commonly detected in human cancers, which was reminiscent of the mixtures of SV40 regulatory region variants identified in simian immunodeficiency virus immunocompromised monkeys. This may indicate that variants of SV40 are more likely to arise or to survive in a host that lacks a robust immune response. Prospective studies are required to answer many questions about infections with polyomaviruses (BKV, JCV, and SV40) in kidney recipients. These include the relative importance of infection by each polyomavirus, the role of primary infection versus reactivation, the means and frequency of monitoring infection, and appropriate therapeutic strategies for polyomaviruses. In addition, it is not known whether polyomaviruses may affect other organ transplant patients. Regis A. Vilchez1 Janet S. Butel Shimon Kusne