title: Adaptive immunity rather than viral cytopathology mediates polyomavirus-associated nephropathy in mice.
abstract: Nephropathy associated with BK polyomavirus causes kidney allograft dysfunction and failure. Understanding the pathogenesis of polyomavirus-associated allograft nephropathy (PVAN) is hampered by the species specificity of Polyomaviridae family members. Using a mouse polyomavirus (MPyV) kidney transplant model, we investigated clinically relevant variables that may contribute to PVAN. We found that the timing and source (i.e. donor vs. recipient) of MPyV infection and the titer of the viral inoculum have significant effects on the extent of allograft injury, with acute infection of the recipient by high-titer MPyV inoculums producing the most profound PVAN. In contrast, altering the degree of MHC matching or increasing ischemia/reperfusion injury by prolonging the cold ischemic time of the allograft did not affect the severity of PVAN. Survival correlated positively with serum creatinine levels, but not with viral loads in the kidney allograft. Using splenectomized alymphoplasia mice, which are unable to mount primary adaptive immune responses, we further demonstrate that persistent high viral loads in the kidney are not sufficient to cause advanced PVAN. These findings suggest that the mechanism of PVAN in mice is not a direct consequence of viral cytopathology, but rather involves interplay between viral infection and the recipient antidonor immune response.
authors.affiliation: Department of Surgery, Emory Transplant Center, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Albrecht
authors.forename: Y
authors.initials: Y
authors.lastname: Dong
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: C
authors.initials: C
authors.lastname: Breeden
authors.forename: A B
authors.initials: AB
authors.lastname: Farris
authors.forename: A E
authors.initials: AE
authors.lastname: Lukacher
authors.forename: K A
authors.initials: KA
authors.lastname: Newell
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D027601:Polyomavirus Infections / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D019562:Viral Load