Cynomolgus polyoma virus infection - A new member of the polyoma virus family causes interstitial nephritis, ureleritis, and enteritis in immunosuppressed cynomolgus monkeys

Polyoma virus infection causes acute interstitial nephritis and ureteral st enosis in humans but has rarely been noted in other species. In the present study, a hitherto unknown polyoma virus was detected in 12 of 57 cynomolgu s monkeys after 3 to 11 weeks of immunosuppression given to promote accepta nce of renal allografts or xenografts, This virus, termed cynomolgus polyom a virus (CPV), is antigenically and genomically related to simian virus 40 (SV40), The tubular epithelial nuclei of the collecting ducts in the medull a and cortex reacted with an antibody for the SV40 large T antigen and by e lectron microscopy contained densely packed paracrystalline arrays of 30- t o 32-nm diameter viral particles. A polymerase chain reaction analysis of D NA extracted from affected kidneys detected polyoma virus sequences using p rimers for a highly conserved region of the large T antigen of polyoma viru s. Sequence analysis showed 7 base substitutions and 3 to 5 deletions in th e 123-nucleotide segment of amplified products, compared with the correspon ding portion of SV40, yielding 84% homology at the amino acid level. CPV ca used interstitial nephritis in six renal allografts, a xenograft kidney, an d six native kidneys. Infected animals showed renal dysfunction and had tub ulointerstitial nephritis with nuclear inclusions, apoptosis, and progressi ve destruction of collecting ducts. CPV was detected in the urothelium of g raft ureters, associated with ureteritis and renal infection, Viral infecti on was demonstrable in smooth muscle cells of the ureteric wall, which show ed apoptosis, One animal had diarrhea and polyoma virus infection in the sm ooth muscle cells of the muscularis propria of the intestine. Spontaneous r esolution occurred in one case; no animal had virus detected in tissues mor e than 3 months after transplantation. Thus, immunosuppression predisposes cynomolgus monkeys to a polyoma virus infection with clinical consequences quite similar to BK virus infection in humans, including renal dysfunction. We also suggest that this may be the pathogenetic basis for the significan t incidence of late onset, isolated ureteral stenosis observed in these rec ipients.