Is the simian virus SV40 associated with idiopathic focal segmental glomerulosclerosis in humans?

BACKGROUND: Glomerulosclerosis was reported in mice transgenic for the simian polyomavirus SV40 early region that contains the transforming sequences encoding the SV40 large T-antigen (TAG). This was discovered when an SV40 epidemic occurred following the use of contaminated polio vaccines during 1955-1963, and led to investigations that showed an association between SV40 infection and tumors in humans. We investigated the possible association of SV40 infection and idiopathic focal segmental glomerulosclerosis (FSGS). METHODS: The study was performed in 17 Bouin-fixed, paraffin-embedded renal biopsies from FSGS patients and 10 matched biopsies from patients with IgA glomerulonephritis; all patients had undergone polio vaccination in the early 1960s. Extracted DNA was polymerase chain reaction (PCR) amplified using SV.for3/SV.rev primers and GabE1/GabE2 primers; both sets of primers map in the region of SV40 TAG sequences, and amplify a fragment of respectively 105-bp and 135-bp. The biopsies considered were those in which the DNA was sufficiently intact to allow amplification of a fragment of 102-bp of the ApoE gene. RESULTS: Three FSGS and none of the IgA biopsies were positive for the SV.for3/SV.rev fragment. Conversely, amplification with GabE1/GabE2 primers did not lead to any specific product in either the IgA or FSGS biopsies. Restriction fragment length polymorphism and sequencing analyses revealed that the positive results obtained with the SV.for3/SV.rev primers were due to amplicons generated by multiple dimerization of forward and reverse primers. CONCLUSIONS: With the limited number of patients investigated, this study excludes the hypothesis that SV40 is associated with idiopathic FSGS.

Thrombotic microangiopathy associated with parvovirus B 19 infection after renal transplantation.

Human parvovirus B19 is considered an etiologic agent of aplastic anemia in immunosuppressed patients. Microscopic vasculitis, with or without renal involvement, has recently been attributed to this viral infection in immunocompetent patients. This study describes four cases of thrombotic renal graft microangiopathy presumably secondary to B19 infection. Twelve to 50 days after transplantation, four patients presented a renal graft dysfunction with creatinine rising to 360 to 1088 micromol/L and requiring hemodialysis in three cases. Renal involvement appeared after a systemic illness characterized by fever, fatigue and arthralgia, aplastic anemia (hemoglobin ranged from 5.3 to 7.8 g/dl), and thrombocytopenia. A thrombotic microangiopathy was observed in the renal biopsies, and the parvovirus B19 genome was isolated by PCR from the specimens. All four patients also became IgM-positive for parvovirus. Three of the four renal biopsies taken at the time of transplantation (T0) from the same patients were found positive for the B19 genome. Graft function recovered, with resolution of the aplastic anemia, within 22 to 110 d. Twenty biopsies performed as routine controls or for suspected acute rejection and nine T0 biopsies of patients with no signs of B19 infection were used. The B19 genome was found in two of 20 posttransplant biopsies and in one of nine T0 biopsies. The temporal association between aplastic anemia and the onset of thrombotic graft microangiopathy, isolation of the viral genome in renal specimens, seroconversion, and endothelial tropism of the virus suggests that B19 could be the etiologic agent of thrombotic microangiopathy in these cases. The development of the disease after infection could depend on other detrimental cofactors, which make the patient more susceptible to microthrombi formation in the renal microvasculature. The renal graft could represent the route of B19 transmission.