With the introduction of immunosuppressive drugs such as tacrolimus and mycophenolate mofetil, the incidence of acute rejection in renal transplantation has fallen to <10 percent at some major medical centers. Unfortunately, these intensive therapeutic regimens increase the risk for viral infections. Of particular concern is the recent emergence of polyomavirus allograft nephropathy (PVAN). PVAN is an inadequately studied and distressing condition that frequently leads to graft loss. Since polyomavirus (PV) is latent in the kidney of up to 50 percent of healthy adults, it is likely that milder forms of PV associated graft dysfunction go unrecognized & untreated, leading to ongoing graft damage and accelerated development of chronic rejection.
The specific aims of this proposal are (1) To characterize the complete clinical spectrum of PV infection, (2) To ascertain the role of viral genotypes, mutations and genetic rearrangements in the evolution of PVAN, (3) To define the cytokine milieu associated with PV infection for potential use in diagnosis and (4) To assess the role of quantitative measurements of viral DNA in the clinical monitoring and follow up of patients with PV infection.
These specific aims will be accomplished by (a) Performing PCR for polyomaviruses BK, JC, and SV4O in clinical samples, (b) Nucleotide sequencing to assign viral genotypes and characterize genetic mutations and rearrangements in the viral genome, (c) Defining blood and renal cytokine expression profiles associated with PV infection, and (d) Using real time quantitative PCR measurements of viral DNA in the blood, urine and kidney tissues to guide clinical management.
| Luo, Chunqing; Hirsch, Hans H; Kant, Jeffrey et al. (2012) VP-1 quasispecies in human infection with polyomavirus BK. J Med Virol 84:152-61 |
| Zhong, Shan; Randhawa, Parmjeet S; Ikegaya, Hiroshi et al. (2009) Distribution patterns of BK polyomavirus (BKV) subtypes and subgroups in American, European and Asian populations suggest co-migration of BKV and the human race. J Gen Virol 90:144-52 |
| Celik, Betul; Randhawa, Parmjeet S (2004) Glomerular changes in BK virus nephropathy. Hum Pathol 35:367-70 |
| Celik, Betul; Shapiro, Ron; Vats, Abhay et al. (2003) Polyomavirus allograft nephropathy: sequential assessment of histologic viral load, tubulitis, and graft function following changes in immunosuppression. Am J Transplant 3:1378-82 |
| Randhawa, Parmjeet; Zygmunt, Debbie; Shapiro, Ron et al. (2003) Viral regulatory region sequence variations in kidney tissue obtained from patients with BK virus nephropathy. Kidney Int 64:743-7 |
