Molecular identification of SV40 infection in human subjects and possible association with kidney disease.
Simian virus 40 (SV40), a monkey polyomavirus that is believed to have entered the human population through contaminated vaccines, is known to be renotropic in simians. If indeed SV40 is endemic within the human population, the route of transmission is unknown. It was therefore hypothesized that SV40 might be renotropic in humans and be detected more frequently in samples obtained from patients with kidney diseases. This study found that typical polyomavirus cytopathic effects (CPE) were present and SV40 T antigen was detected in CV-1 cells cultured with peripheral blood mononuclear cells (PBMC) or urinary cells obtained from patients with kidney disease and healthy volunteers. DNA sequences homologous to the SV40 viral regulatory genome were detected by PCR in urinary cells from 15 (41%) of 36 patients with focal segmental glomerulosclerosis (FSGS), 2 (10%) of 20 patients with other kidney diseases, and 1 (4%) of 22 healthy volunteers (FSGS compared with other glomerular disease, P < 0.02; FSGS compared with healthy volunteers, P = 0.003). SV40 viral regulatory region genome was detected from PBMC at similar frequencies in patients with FSGS (35%), other glomerular diseases (20%), and healthy volunteers (22%). SV40 genome was detected by PCR in kidney tissues from 17 (56%) of 30 of patients with FSGS and 4 (20%) of 20 patients with minimal change disease and membranous nephropathy (P < 0.01). Considerable genetic heterogeneity of the viral regulatory region was detected, which argues against laboratory contamination. SV40 genome was localized to renal tubular epithelial cell nuclei in renal biopsies of patients with FSGS by in situ hybridization. This study demonstrates for the first time that human kidney can serve as a reservoir for SV40 replication and that SV40 may contribute to the pathogenesis of kidney disease, particularly FSGS.
Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1268, USA.
Rui-Mei
RM
Li
Mary H
MH
Branton
Somsak
S
Tanawattanacharoen
Ronald A
RA
Falk
J Charles
JC
Jennette
Jeffrey B
JB
Kopp
D000328:Adult; D000368:Aged; D001483:Base Sequence; D001706:Biopsy; D002478:Cells, Cultured; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D014644:Genetic Variation; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology / Q000821:virology*; D006801:Humans; D017403:In Situ Hybridization; D008181:Lupus Nephritis / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D027601:Polyomavirus Infections / Q000473:pathology / Q000503:physiopathology*; D012045:Regulatory Sequences, Nucleic Acid; D013539:Simian virus 40 / Q000235:genetics / Q000254:growth & development / Q000302:isolation & purification*; D014412:Tumor Virus Infections / Q000473:pathology / Q000503:physiopathology*; D014779:Virus Replication
D004279:DNA, Viral