Skip to main content
Top
Published in: Digestive Diseases and Sciences 7/2010

01-07-2010 | Original Article

JC Virus T-Antigen DNA in Gastrointestinal Mucosa of Immunosuppressed Patients: A Prospective, Controlled Study

Authors: Doron Boltin, Alex Vilkin, Zohar Levi, Ori Elkayam, Yaron Niv

Published in: Digestive Diseases and Sciences | Issue 7/2010

Login to get access

Abstract

Background

JC virus (JCV), a polyoma virus, is the etiological agent of progressive multifocal leukoencephalopathy in immunosuppressed patients. JCV T-Ag has proven oncogenic potential and is expressed in colonic polyps and carcinomas. We proposed that the prevalence of JCV T-Ag DNA is higher in the normal gastrointestinal (GI) mucosa of immunosuppressed patients compared with their immunocompetent counterparts.

Aims

To look for JCV T-Ag DNA in the normal gastrointestinal mucosa of immunosuppressed patients compared with immunocompetent controls.

Methods

Macroscopically normal samples of upper and lower GI mucosa were obtained from 38 immunosuppressed patients. A control group included samples from 19 immunocompetent inflammatory bowel disease (IBD) and 29 non-IBD cases. DNA was extracted and polymerase chain reaction (PCR) was performed using primers specific for T-Ag.

Results

JCV T-Ag DNA was found in nine of the immunosuppressed patients (23.7%) and in three of the controls (6.3%; P = 0.02). Transplant recipients had a particularly high prevalence of JCV T-Ag DNA (35.3%). Patients with IBD receiving immunosuppressive drugs had a higher prevalence of JCV T-Ag DNA in comparison with IBD patients who did not receive immunosuppression (22.2% versus 10.5%, respectively), but this difference was not statistically significant (P = 0.574).

Conclusion

JCV T-Ag DNA is more prevalent in the upper and lower GI mucosa of immunosuppressed patients, possibly indicating that the virus resides in these patients. This may account for the higher prevalence of GI carcinomas in immunosuppressed patients.
Literature
1.
go back to reference Tibbles LA. Reducing the risk of viral infection in renal transplantation. Transplant Proc. 2008;40(10 Suppl):S48–S51.CrossRefPubMed Tibbles LA. Reducing the risk of viral infection in renal transplantation. Transplant Proc. 2008;40(10 Suppl):S48–S51.CrossRefPubMed
2.
go back to reference Morrison VA, Rai KR, Peterson BL. Impact of therapy with chlorambucil, fludarabine, or fludarabine plus chlorambucil on infections in patients with chronic lymphocytic leukemia: Intergroup study cancer and leukemia group B 9011. J Clin Oncol. 2001;19:3611–3621.PubMed Morrison VA, Rai KR, Peterson BL. Impact of therapy with chlorambucil, fludarabine, or fludarabine plus chlorambucil on infections in patients with chronic lymphocytic leukemia: Intergroup study cancer and leukemia group B 9011. J Clin Oncol. 2001;19:3611–3621.PubMed
3.
go back to reference White MK, Khalili K. Polyomaviruses and human cancer: Molecular mechanisms underlying patterns of tumorigenesis. Virology. 2004;324:1–16.CrossRefPubMed White MK, Khalili K. Polyomaviruses and human cancer: Molecular mechanisms underlying patterns of tumorigenesis. Virology. 2004;324:1–16.CrossRefPubMed
4.
go back to reference Raj GV, Gallia GL, Chang CF, Khalili K. T-antigen-dependent transcriptional initiation and its role in the regulation of human neurotropic JC virus late gene expression. J Gen Virol. 1998;79:2147–2155.PubMed Raj GV, Gallia GL, Chang CF, Khalili K. T-antigen-dependent transcriptional initiation and its role in the regulation of human neurotropic JC virus late gene expression. J Gen Virol. 1998;79:2147–2155.PubMed
5.
go back to reference Kitamura T, Kunitake T, Guo J, et al. Transmission of the human polyomavirus JC virus occurs both within the family and outside the family. J Clin Microbiol. 1994;32:2359–2363.PubMed Kitamura T, Kunitake T, Guo J, et al. Transmission of the human polyomavirus JC virus occurs both within the family and outside the family. J Clin Microbiol. 1994;32:2359–2363.PubMed
6.
go back to reference Rossi A, Delbue S, Mazziotti R, et al. Presence, quantitation and characterization of JC virus in the urine of Italian immunocompetent subjects. J Med Virol. 2007;79:408–412.CrossRefPubMed Rossi A, Delbue S, Mazziotti R, et al. Presence, quantitation and characterization of JC virus in the urine of Italian immunocompetent subjects. J Med Virol. 2007;79:408–412.CrossRefPubMed
7.
go back to reference Monaco MC, Atwood WJ, Gravell M, Tornatore CS, Major EO. JC virus infection of hematopoietic progenitor cells, primary B lymphocytes, and tonsillar stromal cells: Implications for viral latency. J Virol. 1996;70:7004–7012.PubMed Monaco MC, Atwood WJ, Gravell M, Tornatore CS, Major EO. JC virus infection of hematopoietic progenitor cells, primary B lymphocytes, and tonsillar stromal cells: Implications for viral latency. J Virol. 1996;70:7004–7012.PubMed
8.
go back to reference Sabath BF, Major EO. Traffic of JC virus from sites of initial infection to the brain: The path to progressive multifocal leukoencephalopathy. J Infect Dis. 2002;186(Suppl 2):S180–S186.CrossRefPubMed Sabath BF, Major EO. Traffic of JC virus from sites of initial infection to the brain: The path to progressive multifocal leukoencephalopathy. J Infect Dis. 2002;186(Suppl 2):S180–S186.CrossRefPubMed
9.
go back to reference Delbue S, Branchetti E, Boldorini R, et al. Presence and expression of JCV early gene large T Antigen in the brains of immunocompromised and immunocompetent individuals. J Med Virol. 2008;80:2147–2152.CrossRefPubMed Delbue S, Branchetti E, Boldorini R, et al. Presence and expression of JCV early gene large T Antigen in the brains of immunocompromised and immunocompetent individuals. J Med Virol. 2008;80:2147–2152.CrossRefPubMed
10.
go back to reference Elsner C, Dorries K. Evidence of human polyomavirus BK and JC infection in normal brain tissue. Virology. 1992;191:72–80.CrossRefPubMed Elsner C, Dorries K. Evidence of human polyomavirus BK and JC infection in normal brain tissue. Virology. 1992;191:72–80.CrossRefPubMed
11.
go back to reference Dorries K. Progressive multifocal leucoencephalopathy: Analysis of JC virus DNA from brain and kidney tissue. Virus Res. 1984;1:25–38.CrossRefPubMed Dorries K. Progressive multifocal leucoencephalopathy: Analysis of JC virus DNA from brain and kidney tissue. Virus Res. 1984;1:25–38.CrossRefPubMed
12.
go back to reference Caldarelli-Stefano R, Vago L, Omodeo-Zorini E, et al. Detection and typing of JC virus in autopsy brains and extraneural organs of AIDS patients and non-immunocompromised individuals. J Neurovirol. 1999;5:125–133.CrossRefPubMed Caldarelli-Stefano R, Vago L, Omodeo-Zorini E, et al. Detection and typing of JC virus in autopsy brains and extraneural organs of AIDS patients and non-immunocompromised individuals. J Neurovirol. 1999;5:125–133.CrossRefPubMed
13.
go back to reference Monaco MC, Jensen PN, Hou J. Detection of JC virus DNA in human tonsil tissue: Evidence for site of initial viral infection. J Virol. 1998;72:9918–9923.PubMed Monaco MC, Jensen PN, Hou J. Detection of JC virus DNA in human tonsil tissue: Evidence for site of initial viral infection. J Virol. 1998;72:9918–9923.PubMed
14.
go back to reference Astrom KE, Mancall EL, Richardson EP. Progressive multifocal leukoencephalopathy: A hitherto unrecognized complication of chronic lymphatic leukaemia and Hodgkin’s disease. Brain. 1958;81:93–111.CrossRefPubMed Astrom KE, Mancall EL, Richardson EP. Progressive multifocal leukoencephalopathy: A hitherto unrecognized complication of chronic lymphatic leukaemia and Hodgkin’s disease. Brain. 1958;81:93–111.CrossRefPubMed
15.
go back to reference Shitrit D, Lev N, Bar-Gil-Shitrit A, Kramer MR. Progressive multifocal leukoencephalopathy in transplant recipients. Transpl Int. 2005;17:658–665.CrossRefPubMed Shitrit D, Lev N, Bar-Gil-Shitrit A, Kramer MR. Progressive multifocal leukoencephalopathy in transplant recipients. Transpl Int. 2005;17:658–665.CrossRefPubMed
16.
go back to reference Boren EJ, Cheema GS, Naguwa SM, Ansari AA, Gershwin ME. The emergence of progressive multifocal leukoencephalopathy (PML) in rheumatic diseases. J Autoimmun. 2008;30:90–98.CrossRefPubMed Boren EJ, Cheema GS, Naguwa SM, Ansari AA, Gershwin ME. The emergence of progressive multifocal leukoencephalopathy (PML) in rheumatic diseases. J Autoimmun. 2008;30:90–98.CrossRefPubMed
17.
go back to reference Kleinschmidt-DeMasters BK, Tyler KL. Progressive Multifocal leucoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med. 2005;353:369–374.CrossRefPubMed Kleinschmidt-DeMasters BK, Tyler KL. Progressive Multifocal leucoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med. 2005;353:369–374.CrossRefPubMed
18.
go back to reference Langer-Gould A, Atlas SW, Bollen AW, Pelletier D. Progressive Multifocal Leukoencephalopathy in a patient treated with natalizumab. N Engl J Med. 2005;35:375–381.CrossRef Langer-Gould A, Atlas SW, Bollen AW, Pelletier D. Progressive Multifocal Leukoencephalopathy in a patient treated with natalizumab. N Engl J Med. 2005;35:375–381.CrossRef
19.
go back to reference Van Assche G, Van Ranst M, Sciot R, et al. Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn’s disease. N Engl J Med. 2005;353:362–368.CrossRefPubMed Van Assche G, Van Ranst M, Sciot R, et al. Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn’s disease. N Engl J Med. 2005;353:362–368.CrossRefPubMed
20.
go back to reference Ferrante P, Caldarelli-Stefano R, Omodeo-Zorini E. Comprehensive investigation of the presence of JC virus in AIDS patients with and without progressive multifocal leukoencephalopathy. J Med Virol. 1997;52:235–242.CrossRefPubMed Ferrante P, Caldarelli-Stefano R, Omodeo-Zorini E. Comprehensive investigation of the presence of JC virus in AIDS patients with and without progressive multifocal leukoencephalopathy. J Med Virol. 1997;52:235–242.CrossRefPubMed
21.
go back to reference Ricciardiello L, Laghi L, Ramamirtham P. JC virus DNA sequences are frequently present in the human upper and lower gastrointestinal tract. Gastroenterology. 2000;119:1228–1235.CrossRefPubMed Ricciardiello L, Laghi L, Ramamirtham P. JC virus DNA sequences are frequently present in the human upper and lower gastrointestinal tract. Gastroenterology. 2000;119:1228–1235.CrossRefPubMed
22.
go back to reference Jung WT, Li MS, Goel A, Boland CR. JC virus T-antigen expression in sporadic adenomatous polyps of the colon. Cancer. 2008;112:1028–1036.CrossRefPubMed Jung WT, Li MS, Goel A, Boland CR. JC virus T-antigen expression in sporadic adenomatous polyps of the colon. Cancer. 2008;112:1028–1036.CrossRefPubMed
23.
go back to reference Selgrad M, Koornstra JJ, Fini L, et al. JC virus infection in colorectal neoplasia that develops after liver transplantation. Clin Cancer Res. 2008;14:6717–6721.CrossRefPubMed Selgrad M, Koornstra JJ, Fini L, et al. JC virus infection in colorectal neoplasia that develops after liver transplantation. Clin Cancer Res. 2008;14:6717–6721.CrossRefPubMed
24.
go back to reference Niv Y, Goel A, Boland CR. JC virus and colorectal cancer: a possible trigger in the chromosomal instability pathways. Curr Opin Gastroenterol. 2005;21:85–89.PubMed Niv Y, Goel A, Boland CR. JC virus and colorectal cancer: a possible trigger in the chromosomal instability pathways. Curr Opin Gastroenterol. 2005;21:85–89.PubMed
25.
go back to reference Enam S, Del Valle L, Lara C, et al. Association of human polyomavirus JCV with colon cancer: Evidence for interaction of viral T-antigen and beta-catenin. Cancer Res. 2002;62:7093–7101.PubMed Enam S, Del Valle L, Lara C, et al. Association of human polyomavirus JCV with colon cancer: Evidence for interaction of viral T-antigen and beta-catenin. Cancer Res. 2002;62:7093–7101.PubMed
26.
go back to reference Laghi L, Randolph AE, Chauhan DP, et al. JC virus DNA is present in the mucosa of the human colon and in colorectal cancers. Proc Natl Acad Sci USA. 1999;96:7484–7489.CrossRefPubMed Laghi L, Randolph AE, Chauhan DP, et al. JC virus DNA is present in the mucosa of the human colon and in colorectal cancers. Proc Natl Acad Sci USA. 1999;96:7484–7489.CrossRefPubMed
27.
go back to reference Ricciardiello L, Baglioni M, Giovannini C. Induction of chromosomal instability in colonic cells by the human polyomavirus JC virus. Cancer Res. 2003;63:7256–7262.PubMed Ricciardiello L, Baglioni M, Giovannini C. Induction of chromosomal instability in colonic cells by the human polyomavirus JC virus. Cancer Res. 2003;63:7256–7262.PubMed
28.
go back to reference Nosho K, Shima K, Kure S, et al. JC virus T-antigen in colorectal cancer is associated with p53 expression and chromosomal instability, independent of CpG island methylator phenotype. Neoplasia. 2009;11:87–95.PubMed Nosho K, Shima K, Kure S, et al. JC virus T-antigen in colorectal cancer is associated with p53 expression and chromosomal instability, independent of CpG island methylator phenotype. Neoplasia. 2009;11:87–95.PubMed
29.
go back to reference Goel A, Li MS, Nagasaka T. Association of JC virus T-antigen expression with the methylator phenotype in sporadic colorectal cancers. Gastroenterology. 2006;130:1950–1961.CrossRefPubMed Goel A, Li MS, Nagasaka T. Association of JC virus T-antigen expression with the methylator phenotype in sporadic colorectal cancers. Gastroenterology. 2006;130:1950–1961.CrossRefPubMed
30.
go back to reference Vanchiere JA, Abudayyeh S, Copeland CM, Lu LB, Graham DY, Butel JS. Polyomavirus shedding in the stool of healthy adults. J Clin Microbiol. 2009;47:2388–2391.CrossRefPubMed Vanchiere JA, Abudayyeh S, Copeland CM, Lu LB, Graham DY, Butel JS. Polyomavirus shedding in the stool of healthy adults. J Clin Microbiol. 2009;47:2388–2391.CrossRefPubMed
31.
go back to reference Boland CR, Bigler J, Newcomb PA, Lampe JW, Potter JD. Evidence for an association between JC virus and colorectal neoplasia. Cancer Epidemiol Biomarkers Prev. 2004;13:2285–2286.PubMed Boland CR, Bigler J, Newcomb PA, Lampe JW, Potter JD. Evidence for an association between JC virus and colorectal neoplasia. Cancer Epidemiol Biomarkers Prev. 2004;13:2285–2286.PubMed
32.
go back to reference Newcomb PA, Bush AC, Stoner GL, Lampe JW, Potter JD, Bigler J. No evidence of an association of JC virus and colon neoplasia. Cancer Epidemiol Biomarkers Prev. 2004;13:662–666.PubMed Newcomb PA, Bush AC, Stoner GL, Lampe JW, Potter JD, Bigler J. No evidence of an association of JC virus and colon neoplasia. Cancer Epidemiol Biomarkers Prev. 2004;13:662–666.PubMed
33.
go back to reference Ricciardiello L, Chang DK, Laghi L, Goel A, Chang CL, Boland CR. Mad-1 is the exclusive JC virus strain present in the human colon, and its transcriptional control region has a deleted 98-base-pair sequence in colon cancer tissues. J Virol. 2001;75:1996–2001.CrossRefPubMed Ricciardiello L, Chang DK, Laghi L, Goel A, Chang CL, Boland CR. Mad-1 is the exclusive JC virus strain present in the human colon, and its transcriptional control region has a deleted 98-base-pair sequence in colon cancer tissues. J Virol. 2001;75:1996–2001.CrossRefPubMed
34.
go back to reference Sanchez W, Talwalkar JA, Gores GJ. Will all liver transplantation patients eventually die from cancer? J Hepatol. 2006;44:13–38.CrossRefPubMed Sanchez W, Talwalkar JA, Gores GJ. Will all liver transplantation patients eventually die from cancer? J Hepatol. 2006;44:13–38.CrossRefPubMed
35.
go back to reference Amital A, Shitrit D, Raviv Y. Development of malignancy following lung transplantation. Transplantation. 2006;81:547–551.CrossRefPubMed Amital A, Shitrit D, Raviv Y. Development of malignancy following lung transplantation. Transplantation. 2006;81:547–551.CrossRefPubMed
36.
go back to reference Nagele H, Bahlo M, Klapdor R, Rodiger W, et al. Tumor marker determination after orthotopic heart transplantation. J Heart Lung Transplant. 1999;18:957–962.CrossRefPubMed Nagele H, Bahlo M, Klapdor R, Rodiger W, et al. Tumor marker determination after orthotopic heart transplantation. J Heart Lung Transplant. 1999;18:957–962.CrossRefPubMed
37.
go back to reference Kasiske BL, Snyder JJ, Gilbertson DT, Wang C. Cancer after kidney transplantation in the United States. Am J Transplant. 2004;4:905–913.CrossRefPubMed Kasiske BL, Snyder JJ, Gilbertson DT, Wang C. Cancer after kidney transplantation in the United States. Am J Transplant. 2004;4:905–913.CrossRefPubMed
38.
go back to reference Rodriguez-Larrain JM, Ziebert JJ, Kfoury AG, Kuwada S, Taylor DO, Renlund DG. Incidence of adenomatous colorectal polyps in cardiac transplant recipients. Transplantation. 1997;64:528–530.CrossRefPubMed Rodriguez-Larrain JM, Ziebert JJ, Kfoury AG, Kuwada S, Taylor DO, Renlund DG. Incidence of adenomatous colorectal polyps in cardiac transplant recipients. Transplantation. 1997;64:528–530.CrossRefPubMed
39.
go back to reference Stewart T, Henderson R, Grayson H, Opelz G. Reduced incidence of rectal cancer compared to gastric and colonic cancer, in a population of 73, 076 men and women chronically immunosuppressed. Clin Cancer Res. 1997;3:51–55.PubMed Stewart T, Henderson R, Grayson H, Opelz G. Reduced incidence of rectal cancer compared to gastric and colonic cancer, in a population of 73, 076 men and women chronically immunosuppressed. Clin Cancer Res. 1997;3:51–55.PubMed
40.
go back to reference Haagsma EB, Hagens VE, Schaapveld M. Increased cancer risk after liver transplantation: A population-based study. J Hepatol. 2001;34:84–91.CrossRefPubMed Haagsma EB, Hagens VE, Schaapveld M. Increased cancer risk after liver transplantation: A population-based study. J Hepatol. 2001;34:84–91.CrossRefPubMed
41.
go back to reference Koornstra JJ, Wesseling J, de Jong AE, Vasen HF, Kleibeuker JH, Haagsma EB. Increased risk of colorectal neoplasia in asymptomatic liver transplant recipients. Gut. 2007;56:892–893.CrossRefPubMed Koornstra JJ, Wesseling J, de Jong AE, Vasen HF, Kleibeuker JH, Haagsma EB. Increased risk of colorectal neoplasia in asymptomatic liver transplant recipients. Gut. 2007;56:892–893.CrossRefPubMed
42.
go back to reference Levitsky J, Miller J, Wang E, et al. Immunoregulatory profiles in liver transplant recipients on different immunosuppressive agents. Hum Immunol. 2009;70:146–150.CrossRefPubMed Levitsky J, Miller J, Wang E, et al. Immunoregulatory profiles in liver transplant recipients on different immunosuppressive agents. Hum Immunol. 2009;70:146–150.CrossRefPubMed
43.
go back to reference Hodge G, Hodge S, Reynolds P, Holmes M. Intracellular cytokines in blood T cells in lung transplant patients—a more relevant indicator of immunosuppression than drug levels. Clin Exp Immunol. 2005;139:159–164.CrossRefPubMed Hodge G, Hodge S, Reynolds P, Holmes M. Intracellular cytokines in blood T cells in lung transplant patients—a more relevant indicator of immunosuppression than drug levels. Clin Exp Immunol. 2005;139:159–164.CrossRefPubMed
Metadata
Title
JC Virus T-Antigen DNA in Gastrointestinal Mucosa of Immunosuppressed Patients: A Prospective, Controlled Study
Authors
Doron Boltin
Alex Vilkin
Zohar Levi
Ori Elkayam
Yaron Niv
Publication date
01-07-2010
Publisher
Springer US
Published in
Digestive Diseases and Sciences / Issue 7/2010
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI
https://doi.org/10.1007/s10620-009-0986-y

Other articles of this Issue 7/2010

Digestive Diseases and Sciences 7/2010 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine