Male, 2-year old, Cynomolgus monkey (Macaca fascicularis)This monkey was euthanized at the end of a 14 day toxicity study. There were no clinical observations.
This is a section of kidney characterized by widespread, multifocal, peritubular infiltrates of predominantly lymphocytes and plasma cells.Â Adjacent tubules are often lined by epithelial cells with enlarged hyperchromatic nuclei or epithelial cells that are in various stages of degeneration and sloughing.Â Lymphoplasmacytic infiltrates are also present within or obliterate tubules and tubular basement membranes are breached.Â Rarely, large, eosinophilic, intranuclear inclusion bodies are present within tubular epithelial cells.
Kidney: Interstitial nephritis, lymphoplasmacytic, multifocal, moderate with epithelial intranuclear inclusions.
The histopathology and presence of intraculear inclusions are consistent with a viral etiology, in particular polyoma virus.Â Several simian polyomas viruses have been described and compared to the JC and BK polyoma viruses in humans
In this study, several monkeys in vehicle-treated groups as well as test-article treated groups had interstitial nephritis.Â Several female monkeys in this study also had mononuclear infiltrates (inflammation) of the smooth muscle of the gastrointestinal tract as evidence of infection, with no relationship to dose of test articles.Â Additionally, there were no clinical chemistry changes associated with renal disease or infection.Â Thus, we interpreted these findings to be incidental to the study
Kidney: Nephritis, interstitial, lymphoplasmacytic, multifocal to coalescing, moderate, with multifocal tubular epithelial karyomegaly and rare intranuclear inclusion bodies, Cynomolgus monkey (Macaca fascicularis), primate.
Polyoma viruses and papilloma viruses are double stranded DNA viruses belonging to the Papovaviridae family of viruses.Â Several polyoma viruses, including SV40, simian agent 12, polyoma virus papionis-2 and lymphotropic papovavirus, infect old world primates.Â Closely related polyoma viruses in humans include BK polyoma virus and JC polyoma virus.Â All polyoma viruses share two regulatory proteins, known as the large T and small T antigen, which can serve as primers in PCR identification.1 Clinically overt disease due to polyomaviruses are commonly associated with immunosuppression, often as a result of either infection with Simian Immunodeficiency Virus or the use of immunosuppressive drugs.
Cynomolgus Polyoma Virus, antigenically and genomically related to Simian Virus 40, has been reported to cause renal dysfunction and tubulointerstitial nephritis in immunosuppressed Cynomolgus monkeys.Â Intranuclear inclusions within karyomegalic (2-3X normal) tubular epithelial cells were a consistent finding within affected kidneys.1
The differential diagnosis for these inclusions includes cytomegalovirus with characteristic large, dense, intranuclear inclusions often surrounded by a halo (owls eye cells), and adenovirus with very large intranuclear inclusions that are deeply basophilic, "smudgy", and not surrounded by a clear halo.
1.Â van Gorder MA, Pelle PD, Henson JW, Sachs DH, Cosimi AB, Colvin RB: Cynomolgus Polyoma Virus infection: a new member of the Polyoma Virus family causes interstitial nephritis, ureteritis, and enteritis in immunosuppressed Cynomolgus monkeys.Â Am J Pathol 154:1273-1284, 1999