Adaptive immunity rather than viral cytopathology mediates polyomavirus-associated nephropathy in mice

J. A. Albrecht, Y. Dong, J. Wang, C. Breeden, A. B. Farris, A. E. Lukacher, K. A. Newell

Research output: Contribution to journalArticle

9 Scopus citations

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. Experiments using a mouse kidney transplant model of polyomavirus infection demonstrate that an intact adaptive immune system is necessary for the development of polyomavirus-associated nephropathy, suggesting that viral cytolysis is insufficient to mediate renal injury in this model.

Original languageEnglish (US)
Pages (from-to)1419-1428
Number of pages10
JournalAmerican Journal of Transplantation
Volume12
Issue number6
DOIs
StatePublished - Jun 2012

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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