Polyomaviruses and disease: is there more to know than viremia and viruria?

Current Opinion in Organ Transplantation

Volumn 20, Issue 3, 2015, Pages 348-358

  Nickeleit, Volker ^a   Singh, Harsharan K ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

Biomarker; BK virus; Classification; Electron microscopy; Haufen; Outcome; Pathology; Polyomavirus nephropathy; Transplantation; Urine

Indexed keywords

BIOLOGICAL MARKER;

AIDS PATIENT; BK VIRUS; BONE MARROW TRANSPLANTATION; CANCER GROWTH; CANCER PATIENT; CARCINOGENESIS; CELLULAR IMMUNITY; DIAGNOSIS; DIAGNOSTIC ACCURACY; ELECTRON MICROSCOPY; HUMAN; INJURY; KIDNEY DISEASE; KIDNEY TRANSPLANTATION; MRNA EXPRESSION LEVEL; PATIENT CARE; POLYOMAVIRUS; POLYOMAVIRUS ASSOCIATED NEPHROPATHY; PRIORITY JOURNAL; REVIEW; SALIVARY GLAND DISEASE; VIREMIA; ADVERSE EFFECTS; ANIMAL; BLOOD; KIDNEY DISEASES; POLYOMAVIRUS INFECTIONS; URINE;

ANIMALS; BK VIRUS; HUMANS; KIDNEY DISEASES; KIDNEY TRANSPLANTATION; POLYOMAVIRUS INFECTIONS; VIREMIA;

EID: 84979852082     PISSN: 10872418     EISSN: 15317013     Source Type: Journal    
DOI: 10.1097/MOT.0000000000000192     Document Type: Review

References (85)

1. Rinaldo CH, Hirsch HH. The human polyomaviruses: from orphans and mutants to patchwork family. Acta Pathol Microbiol Immunol Scand 2013; 121:681–684.
2. Mishra N, Pereira M, Rhodes RH, et al. Identification of a novel polyomavirus in & a pancreatic transplant recipient with retinal blindness and vasculitic myopathy. J Infect Dis 2014; 210:1595–1599. This is the first description of a novel polyomavirus strain with possible tropism for vascular endothelium commonly not seen in productive polyomavirus infections.
3. Dalianis T, Hirsch HH. Human polyomaviruses in disease and cancer. Virology && 2013; 437:63–72. An excellent up-to-date overview of the various human polyomaviruses identified thus far and their role in driving disease and cancer.
4. Husseiny MI, Anastasi B, Singer J, Lacey SF. A comparative study of Merkel cell, BK and JC polyomavirus infections in renal transplant recipients and healthy subjects. J Clin Virol 2010; 49:137–140.
5. van der Meijden E, Wunderink HF, van der Blij-de Brouwer CS, et al. Human polyomavirus 9 infection in kidney transplant patients. Emerg Infect Dis 2014; 20:991–999.
6. Hirsch HH, Babel N, Comoli P, et al. European perspective on human && polyomavirus infection, replication and disease in solid organ transplantation. Clin Microbiol Infect 2014; 20 (Suppl 7):74–88. This is a comprehensive article discussing human polyomaviruses in solid-organ transplant recipients, and current recommendations for screening, management, and treatment of the various human diseases caused by polyomaviruses with particular focus on PVN.
7. Bloomgren G, Richman S, Hotermans C, et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med 2012; 366: 1870–1880.
8. Rinaldo CH, Tylden GD, Sharma BN. The human polyomavirus BK (BKPyV): virological background and clinical implications. Acta Pathol Microbiol Immunol Scand 2013; 121:728–745.
9. Jeffers L, Webster-Cyriaque JY. Viruses and salivary gland disease (SGD): lessons from HIV SGD. Adv Dental Res 2011; 23:79–83.
10. Burger-Calderon R, Madden V, Hallett RA, et al. Replication of oral BK virus in & human salivary gland cells. J Virol 2014; 88:559–573. This article describes BKV infections of salivary gland cells and the potential role for BKV in the development of salivary gland disease in immunocompromised HIV-infected patients. Data suggest a role for BKV and productive infections in disease processes outside the urogenital tract with BK shedding into body fluids.
11. Laskin BL, Denburg M, Furth S, et al. BK viremia precedes hemorrhagic && cystitis in children undergoing allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2013; 19:1175–1182. This is the largest series of pediatric patients who received hematopoetic stem cell transplants in which plasma samples were collected prospectively and BK viral load levels measured systematically. The findings demonstrate a very strong association of BK viremia and the development of hemorrhagic cystitis. Data also underscore that BK viremia can originate from sites other than the kidney itself.
12. Coursaget P, Samimi M, Nicol JT, et al. Human Merkel cell polyomavirus: virological background and clinical implications. Acta Pathol Microbiol Immunol Scand 2013; 121:755–769.
13. Carter JJ, Paulson KG, Wipf GC, et al. Association of Merkel cell polyomavirus-specific antibodies with Merkel cell carcinoma. J Natl Cancer Inst 2009; 101:1510–1522.
14. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science (New York, NY) 2008; 319:1096–1100.
15. Kassem A, Schopflin A, Diaz C, et al. Frequent detection of Merkel cell polyomavirus in human Merkel cell carcinomas and identification of a unique deletion in the VP1 gene. Cancer Res 2008; 68:5009–5013.
16. Viscidi RP, Rollison DE, Sondak VK, et al. Age-specific seroprevalence of Merkel cell polyomavirus, BK virus, and JC virus. Clin Vaccine Immunol 2011; 18:1737–1743.
17. Matthews MR, Wang RC, Reddick RL, et al. Viral-associated trichodysplasia spinulosa: a case with electron microscopic and molecular detection of the trichodysplasia spinulosa-associated human polyomavirus. J Cutaneous Pathol 2011; 38:420–431.
18. van der Meijden E, Kazem S, Burgers MM, et al. Seroprevalence of trichodysplasia spinulosa-associated polyomavirus. Emerg Infect Dis 2011; 17: 1355–1363.
19. Geetha D, Tong BC, Racusen L, et al. Bladder carcinoma in a transplant recipient: evidence to implicate the BK human polyomavirus as a causal transforming agent. Transplantation 2002; 73:1933–1936.
20. Gardner SD, Field AM, Coleman DV, Hulme B. New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet 1971; 1:1253–1257.
21. Padgett BL, Walker DL, ZuRhein GM, et al. Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet 1971; 1:1257–1260.
22. Gosert R, Kardas P, Major EO, Hirsch HH. Rearranged JC virus noncoding control regions found in progressive multifocal leukoencephalopathy patient samples increase virus early gene expression and replication rate. J Virol 2010; 84:10448–10456.
23. Khanna N, Wolbers M, Mueller NJ, et al. JC virus-specific immune responses in human immunodeficiency virus type 1 patients with progressive multifocal leukoencephalopathy. J Virol 2009; 83:4404–4411.
24. Schroder A, Lee DH, Hellwig K, et al. Successful management of natalizumab-associated progressive multifocal leukoencephalopathy and immune reconstitution syndrome in a patient with multiple sclerosis. Arch Neurol 2010; 67:1391–1394.
25. Hirsch HH, Kardas P, Kranz D, Leboeuf C. The human JC polyomavirus (JCPyV): virological background and clinical implications. Acta Pathol Microbiol Immunol Scand 2013; 121:685–727.
26. Maginnis MS, Nelson CD, Atwood WJ. JC polyomavirus attachment, entry, and trafficking: unlocking the keys to a fatal infection. J Neurovirol 2014. [Epub ahead of print]
27. Sharma SG, Nickeleit V, Herlitz LC, et al. BK polyoma virus nephropathy in the & native kidney. Nephrol Dialysis Transplant 2013; 28:620–631. This is a series of eight cases of PVN diagnosed in native kidneys; pathologic features, risk factors, and outcome data are discussed.
28. Hirsch HH, Randhawa P. BK polyomavirus in solid organ transplantation. Am J Transplant 2013; 13 (Suppl 4):179–188.
29. Nickeleit V, Colvin RB, Mengel M. Renal transplant pathology. In: Jennette JC, Olson JL, D’Agati VD, Silva FG, editors. Heptinstall’s pathology of the kidney. 2. Philadelphia, PA: Lippincott, Williams & Wilkins; 2014. pp. 1441–1446.
30. Singh H, Andreoni KA, Madden V, et al. Presence of urinary haufen accurately predicts polyomavirus nephropathy. J Am Soc Nephrol 2009; 20:416–427.
31. Singh HK, Reisner H, Derebail VK, et al. Polyomavirus nephropathy: quanti- && tative urinary polyomavirus-haufen testing accurately predicts the degree of intrarenal viral disease. Transplantation 2015; 99:609–615. This paper describes the utility of a novel non-invasive assay for PVN, the urinary polyomavirus-Haufen test, with special emphasis on quantitative test results. The authors report that the number of cast-like polyomavirus Haufen per ml of urine tightly correlates with the severity of ‘intra renal’ polyomavirus nephropathy. Such correlation is, in comparison, not seen with quantitative PCR assays for BK-viremia and viruria. The findings shed serious doubts on the common clinical practice of assuming that BK viremia levels and PCR results accurately reflect the degree of virally induced renal injury.
32. Singh HK, Donna Thompson B, Nickeleit V. Viral Haufen are urinary biomarkers of polyomavirus nephropathy: new diagnostic strategies utilizing negative staining electron microscopy. Ultrastruct Pathol 2009; 33:222–235.
33. Adam B, Randhawa P, Chan S, et al. Banff initiative for quality assurance in & transplantation (BIFQUIT): reproducibility of polyomavirus immunohistochemistry in kidney allografts. Am J Transplant 2014; 14:2137–2147. This is a large multicenter reproducibility study mainly evaluating the immunohistochemical staining and scoring of SV40 large T antigen on tissue. Results confirm the diagnostic role of immunostains for SV40-T as a reliable marker for PVN.
34. Sharif A, Alachkar N, Bagnasco S, et al. Incidence and outcomes of BK virus allograft nephropathy among ABO- and HLA-incompatible kidney transplant recipients. Clin J Am Soc Nephrol 2012; 7:1320–1327.
35. Sharif A, Alachkar N, Kraus E. Incompatible kidney transplantation: a brief overview of the past, present and future. QJM 2012; 105:1141–1150.
36. Sood P, Senanayake S, Sujeet K, et al. Management and outcome of BK viremia in renal transplant recipients: a prospective single-center study. Transplantation 2012; 94:814–821.
37. Li YJ, Weng CH, Lai WC, et al. A suppressive effect of cyclosporine A on replication and noncoding control region activation of polyomavirus BK virus. Transplantation 2010; 89:299–306.
38. Binet I, Nickeleit V, Hirsch HH, et al. Polyomavirus disease under new immunosuppressive drugs: a cause of renal graft dysfunction and graft loss. Transplantation 1999; 67:918–922.
39. Nickeleit V, Hirsch HH, Zeiler M, et al. BK-virus nephropathy in renal transplants-tubular necrosis, MHC-class II expression and rejection in a puzzling game. Nephrol Dialysis Transplant 2000; 15:324–332.
40. Hirsch HH, Vincenti F, Friman S, et al. Polyomavirus BK replication in de novo kidney transplant patients receiving tacrolimus or cyclosporine: a prospective, randomized, multicenter study. Am J Transplant 2013; 13:136–145.
41. Brennan DC, Agha I, Bohl DL, et al. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant 2005; 5:582–594.
42. Trydzenskaya H, Juerchott K, Lachmann N, et al. The genetic predisposition of natural killer cell to BK virus-associated nephropathy in renal transplant patients. Kidney Int 2013; 84:359–365.
43. Womer KL, Huang Y, Herren H, et al. Dendritic cell deficiency associated with development of BK viremia and nephropathy in renal transplant recipients. Transplantation 2010; 89:115–123.
44. Schmidt T, Adam C, Hirsch HH, et al. BK polyomavirus-specific cellular && immune responses are age-dependent and strongly correlate with phases of virus replication. Am J Transplant 2014; 14:1334–1345. A comprehensive study demonstrating the age-dependent cellular immune responses to BK polyomavirus in both immunocompetent adults and patients with renal transplants emphasizing the role of T-cell responses and cytokine expression in regulating polyomaviruses replication.
45. Prosser SE, Orentas RJ, Jurgens L, et al. Recovery of BK virus large T-antigen-specific cellular immune response correlates with resolution of BK virus nephritis. Transplantation 2008; 85:185–192.
46. Comoli P, Hirsch HH, Ginevri F. Cellular immune responses to BK virus. Curr Opin Organ Transplant 2008; 13:569–574.
47. Schachtner T, Muller K, Stein M, et al. BK virus-specific immunity kinetics: a predictor of recovery from polyomavirus BK-associated nephropathy. Am J Transplant 2011; 11:2443–2452.
48. Binggeli S, Egli A, Schaub S, et al. Polyomavirus BK-specific cellular immune response to VP1 and large T-antigen in kidney transplant recipients. Am J Transplant 2007; 7:1131–1139.
49. Mani J, Jin N, Schmitt M. Cellular immunotherapy for patients with reactivation of JC and BK polyomaviruses after transplantation. Cytotherapy 2014; 16:1325–1335.
50. Vasudev B, Hariharan S, Hussain SA, et al. BK virus nephritis: risk factors, timing, and outcome in renal transplant recipients. Kidney Int 2005; 68:1834–1839.
51. Ramos E, Drachenberg CB, Papadimitriou JC, et al. Clinical course of polyoma virus nephropathy in 67 renal transplant patients. J Am Soc Nephrol 2002; 13:2145–2151.
52. Schwarz A, Linnenweber-Held S, Heim A, et al. Factors influencing viral clearing and renal function during polyomavirus BK-associated nephropathy after renal transplantation. Transplantation 2012; 94:396–402.
53. Jacobi J, Prignitz A, Buttner M, et al. BK viremia and polyomavirus nephropathy in 352 kidney transplants; risk factors and potential role of mTOR inhibition. BMC Nephrol 2013; 14:207.
54. Haas M, Sis B, Racusen LC, et al. Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant 2014; 14:272–283.
55. Nickeleit V, Mihatsch MJ. Polyomavirus allograft nephropathy and concurrent acute rejection: a diagnostic and therapeutic challenge. Am J Transplant 2004; 4:838–839.
56. Menter T, Mayr M, Schaub S, et al. Pathology of resolving polyomavirus- && associated nephropathy. Am J Transplant 2013; 13:1474–1483. This is the first large biopsy-based series of patients with resolving/healed PVN evaluating histologic features, clinical presentation, and treatment strategies. The authors discuss the concept of immune reconstitution type of graft inflammation and outline potential diagnostic and therapeutic implications.
57. Dadhania D, Snopkowski C, Ding R, et al. Validation of noninvasive diagnosis of BK virus nephropathy and identification of prognostic biomarkers. Transplantation 2010; 90:189–197.
58. Drachenberg CB, Papadimitriou JC, Hirsch HH, et al. Histological patterns of polyomavirus nephropathy: correlation with graft outcome and viral load. Am J Transplant 2004; 4:2082–2092.
59. Schaub S, Mayr M, Egli A, et al. Transient allograft dysfunction from immune reconstitution in a patient with polyoma BK-virus-associated nephropathy. Nephrol Dialysis Transplant 2007; 22:2386–2390.
60. Hirsch HH, Brennan DC, Drachenberg CB, et al. Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations. Transplantation 2005; 79:1277–1286.
61. Dadhania D, Snopkowski C, Ding R, et al. Epidemiology of BK virus in renal allograft recipients: independent risk factors for BK virus replication. Transplantation 2008; 86:521–528.
62. Nickeleit V, True K, Detwiler R, et al. Risk assessment for polyomavirus nephropathy using urine cytology and the detection of decoy cells: cheap and efficient. Transplantation 2012; 94:e42–e44.
63. Chakera A, Dyar OJ, Hughes E, et al. Detection of polyomavirus BK reactivation after renal transplantation using an intensive decoy cell surveillance program is cost-effective. Transplantation 2011; 92:1018–1023.
64. Rorije NM, Shea MM, Satyanarayana G, et al. BK virus disease after allogeneic stem cell transplantation: a cohort analysis. Biol Blood Marrow Transplant 2014; 20:564–570.
65. Gilis L, Morisset S, Billaud G, et al. High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2014; 49:664–670.
66. Razonable RR, Brown RA, Humar A, et al. A longitudinal molecular surveillance study of human polyomavirus viremia in heart, kidney, liver, and pancreas transplant patients. J Infect Dis 2005; 192:1349–1354.
67. Hassan S, Mittal C, Amer S, et al. Currently recommended BK virus (BKV) plasma viral load cutoff of 4 log10/mL underestimates the diagnosis of BKV-associated nephropathy: a single transplant center experience. Transplant Infect Dis 2014; 16:55–60.
68. Renoult E, Coutlee F, Paquet M, et al. Evaluation of a preemptive strategy for BK polyomavirus-associated nephropathy based on prospective monitoring of BK viremia: a kidney transplantation center experience. Transplant Proc 2010; 42:4083–4087.
69. Knight RJ, Gaber LW, Patel SJ, et al. Screening for BK viremia reduces but & does not eliminate the risk of BK nephropathy. Transplantation 2013; 95: 949–954. The article outlines single-center results on screening for BK viremia and protocols for minimization of immunosuppression. Therapeutic intervention could not prevent graft failure in patients with BK viremia when compared with controls. These data might suggest the lack of therapeutic benefits in patients with ‘presumptive’ PVN treated preemptively. Unfortunately, however, data analysis does not allow for a clear distinction between patients with ‘presumptive’ and ‘definitive’ PVN, and PVN disease grades are unknown.
70. Nickeleit V, Brylawski B, Rivier L, Singh HK. Urinary polyomavirus-haufen shedding in mouse and man: a proof-of-concept study for a non-invasive urine biomarker for polyomavirus nephropathy. Modern Pathol 2013; 26:390A.
71. Ding R, Medeiros M, Dadhania D, et al. Noninvasive diagnosis of BK virus nephritis by measurement of messenger RNA for BK virus VP1 in urine. Transplantation 2002; 74:987–994.
72. Dadhania D, Snopkowski C, Muthukumar T, et al. Noninvasive prognostication && of polyomavirus BK virus-associated nephropathy. Transplantation 2013; 96:131–138. In patients with ‘definitive’ PVN, urinary cell levels of mRNA for plasminogen activator inhibitor-1 and serum creatinine levels at time of initial PVN diagnosis are independent prognosticators of graft failure. Data outline noninvasive diagnostic strategies for diagnosis and prognosis of PVN.
73. Almeras C, Vetromile F, Garrigue V, et al. Monthly screening for BK viremia is an effective strategy to prevent BK virus nephropathy in renal transplant recipients. Transplant Infect Dis 2011; 13:101–108.
74. Schaub S, Hirsch HH, Dickenmann M, et al. Reducing immunosuppression preserves allograft function in presumptive and definitive polyomavirus-associated nephropathy. Am J Transplant 2010; 10:2615–2623.
75. Rollison DE, Sexton WJ, Rodriguez AR, et al. Lack of BK virus DNA sequences in most transitional-cell carcinomas of the bladder. Int J Cancer 2007; 120:1248–1251.
76. Roberts IS, Besarani D, Mason P, et al. Polyoma virus infection and urothelial carcinoma of the bladder following renal transplantation. Br J Cancer 2008; 99:1383–1386.
77. Narayanan M, Szymanski J, Slavcheva E, et al. BK virus associated renal cell carcinoma: case presentation with optimized PCR and other diagnostic tests. Am J Transplant 2007; 7:1666–1671.
78. Alexiev BA, Randhawa P, Vazquez Martul E, et al. BK virus-associated urinary bladder carcinoma in transplant recipients: report of 2 cases, review of the literature, and proposed pathogenetic model. Hum Pathol 2013; 44:908–917.
79. Nickeleit V, Singh HK, Goldsmith CS, et al. BK virus-associated urinary bladder carcinoma in transplant recipients: productive or nonproductive polyomavirus infections in tumor cells? Hum Pathol 2013; 44:2870–2871.
80. Uhm J, Hamad N, Michelis FV, et al. The risk of polyomavirus BK-associated hemorrhagic cystitis after allogeneic hematopoietic SCT is associated with myeloablative conditioning, CMV viremia and severe acute GVHD. Bone Marrow Transplant 2014; 49:1528–1534.
81. Erard V, Storer B, Corey L, et al. BK virus infection in hematopoietic stem cell transplant recipients: frequency, risk factors, and association with postengraftment hemorrhagic cystitis. Clin Infect Dis 2004; 39:1861–1865.
82. Lekakis LJ, Macrinici V, Baraboutis IG, et al. BK virus nephropathy after allogeneic stem cell transplantation: a case report and literature review. Am J Hematol 2009; 84:243–246.
83. Limaye AP, Smith KD, Cook L, et al. Polyomavirus nephropathy in native kidneys of nonrenal transplant recipients. Am J Transplant 2005; 5:614–620.
84. Hingorani S. Chronic kidney disease in long-term survivors of hematopoietic cell transplantation: epidemiology, pathogenesis, and treatment. J Am Soc Nephrol 2006; 17:1995–2005.
85. Ellis MJ, Parikh CR, Inrig JK, et al. Chronic kidney disease after hematopoietic cell transplantation: a systematic review. Am J Transplant 2008; 8:2378–2390.