JC Polyomavirus Infections in Transplant Patients

The polyomavirus JC virus (JCV) is a small nonenveloped DNA virus that asymptomatically infects about 80% of healthy adults and establishes latency in the kidney tissue. In case of immunodeficient hosts, JCV can lytically infect the oligodendrocytes, causing a fatal demyelinating disease, known as Progressive Multifocal Leukoencephalopathy (PML). Although the reactivation of another human polyomavirus, BK Virus (BKV), is relatively common and its association with the Polyomavirus Associated Nephropathy (PVAN) following renal transplantation is assessed, JCV replication and its impact on graft function and survival is less well studied. In addition, none of the performed studies ruled out the hypothesis that JCV could be associated with certain post-transplantation clinical syndromes. Thus, monitoring of Polyomaviruses infection, especially during the first 24 months post-transplantation, is recommended. *Corresponding author: Mariano Ferraresso, Department of General and Vascular Surgery, St. Joseph Hospital-IRCCS-Multimedia, Via San Vittore 12, 20122 Milan, Italy, Fax: +39 0250320393; Tel: +39 0250320382; E-mail: [email protected] Received October 01, 2012; Accepted October 04, 2012; Published October 12, 2012 Citation: Delbue S, Ferraresso M (2012) JC Polyomavirus Infections in Transplant Patients. J Transplant Technol Res 2:e114. doi:10.4172/2161-0991.1000e114 Copyright: © 2012 Delbue S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. JC virus (JCV) is a member of the Polyomaviridae family, including naked DNA viruses with icosahedral capsids and small, circular, double-stranded DNA genomes. The natural hosts for polyomaviruses include humans, other primates, rodents, rabbits and birds [1]. Padgett et al. first isolated it in 1971 from the brain of a patient with the initial J.C., affected by Hodgkin’s Lymphoma who died of Progressive Multifocal Leukoencephalopathy (PML), a demyelinating disease of the Central Nervous System (CNS) [2]. PML is a rare disease characterized by the lytic infection of glial cells and is often fatal. The disease occurs almost exclusively in patients with severe immunodeficiency; consequently the incidence of PML has increased dramatically, following the spread of HIV/AIDS. Nowadays, HIV infection is still the most frequent setting for PML, ~80% of the cases, followed by hematologic malignancies (~8%), solid cancers (~3%), organ transplantation and autoimmune diseases treated with immunomodulators [3]. Indeed, successful treatments for PML are not currently available. JCV does not infect any species other than humans and its ability to infect human cells may be restricted at the level of viral early gene transcription and DNA replication, with the protein named Large T Antigen (Tag) interacting specifically with the human DNA polymerase [4]. JCV has a tropism for replication in human glial cells, kidney epithelial cells and, with a less efficiency, in B lymphocytes, and the restricted CNS tropism is confirmed by both experimental animals and in vitro analysis [4,5]. The transmission of JCV is not fully understood. JCV-specific antibodies are detected in approximately 80% of adults and the primary infection occurs in early childhood, usually in an asymptomatic way and results in a primary viremia. Afterwards, the virus produces a persistent latent infection in the kidney and is shed into the urine. Since JCV may be detected in the tonsillar stromal cells, viral transmission via the respiratory route has been hypothesized, and the virus isolation in B lymphocytes suggested the lymphoid tissue as another site of viral latency with lymphocytes involved in viral circulatory dissemination to other anatomic sites [6,7]. The virus has also been detected in the gastrointestinal tract and in the raw urban sewage suggesting a possible oral or fecal transmission of JCV [8,9]. In the context of an immunosuppressive condition, such as AIDS and transplantation, JCV disseminates to the CNS and litically infects oligodendrocytes, causing the PML. Another hypothesis that explains the pathogenesis of PML states that: JCV may establish latency in normal brain tissue and reactivates in non immunocompetent hosts [10-12]. Reports of JCV infection in renal transplant recipients have been published immediately after the first isolation of the virus [13,14]. Since those times, subsequent works have investigated both the silent and the symptomatic infection and/or reactivation of JCV in the setting of kidney transplantation, finding contradictory results. Gardner and colleagues performed a wide prospective, serological study for the evidence of JCV infection in forty eight renal transplant recipients, finding that 54% of the patients were seropositive already before the operation, and that in 23% of the seronegative patients JCV infection occurred within the first three months after transplantation [15]. Molecular analysis were also conducted, by means of specific in situ Hybridization, PCR and Quantitative PCR assays by different international groups: JCV has been identified in kidney biopsy tissue and/or urine within a range of 3.4% and 46% of kidney transplanted patients, while JCV viremia ranged from 0% and 25% [16-24]. The most recent surveys, that had the possibility to measure the amount of replicating JCV in the clinical specimens, reported a very wide range of viral loads, from 2.0 ×103 copies/ml to 1 × 107 copies/ml [17,19,21,22,24,25]. Only few studies analyzed also the molecular features of the isolated virus, observing that the JCV strains infecting the kidney transplantation recipients did not differ significantly from those infecting the immunocompetent subjects [21,25,26]. Regarding the non-kidney solid organ transplants (SOT), the incidence and clinical manifestation of JCV infection have been poorly investigated. In 2005, two independent groups published very different results about JCV infection in liver transplant patients, reporting 1.7% and 22.7% of patients excreting the virus, respectively [24,27]. More recently, Kusne and colleagues observed that 71% of the studied patients excreted JCV after liver transplantation, with very high viral load (1.6 × 106 copies/ml) [28]. Studies on the association between JCV infection and lung, pancreas and heart transplantations are even rarer. Journal of Transplantation Technologies & Research