Viral infection in bone marrow transplants: Is JC virus involved?

Abstract

Hemorrhagic cystitis is characterized by hematuria due to inflammation of the bladder. In bone marrow transplants, this disease is linked to the infection by human polyomavirus BK, whereas the role of the human polyomavirus JC is unclear. The transcriptional control regions of both viruses contain important cellular transcription factor binding sites that undergo rearrangement process generating suitable variants that could be more active for viral replication and for the onset of hemorrhagic cystitis. In this study urine obtained from seven patients with bone marrow transplant were examined. Polyomavirus genomes were quantified by PCR and viral loads were compared. The transcriptional regions of both viruses were amplified and sequenced to determine the presence of variants. Subtypes of polyomaviruses were determined by amplification and sequencing of the viral protein 1 region. The results showed that four of seven patients were positive for BK DNA, two of seven patients had BK and JC DNA and one of seven had JC DNA. Positive samples were amplified and sequenced successively for transcriptional regions. The viral archetype was always found in both viruses. Finally, typing showed that BK virus subtype I infected patients with BK, whereas JC virus genotype IA and genotype 1B were found in patients infected with JC. The data suggest that new and different approaches are required to improve the morbidity and mortality caused by polyoma-associated hemorrhagic cystitis, since it known that BK virus is involved in the onset of hemorrhagic cystitis, whereas the role of JC virus should be investigated further.

Polyomavirus JC reactivation and noncoding control region sequence analysis in pediatric Crohn's disease patients treated with infliximab

“…Moreover, all the rearrangements detected at t3 are completely random, as revealed by the VP1 genotype analysis performed on these 7 patients. In fact, the VP1 genotype analysis showed the presence of genotype 1A in 5 patients and the presence of genotype 1B in 2 patients (data not shown), in agreement with the most common genotypes detected in the European population as described by some Authors (Agostini et al 2001;Mischitelli et al 2010). The finding of these rearranged JCV NCCR sequences at t3 could be explained by the interference of infliximab in the regulation of the fine balance between anti-inflammatory drug benefit and immune surveillance, also taking into account the timing of administration of this mAb during the maintenance therapeutic program.…”

Human Polyomavirus JC monitoring and noncoding control region analysis in dynamic cohorts of individuals affected by immune-mediated diseases under treatment with biologics: an observational study

“…Although other author found a significant association between the JCPyV Type 2 and infliximab treatment in a pediatric CD cohort [57], we did not observed a correlation between rearranged JCPyV NCCR sequences and a particular JCPyV genotype in each enrolled cohort. Conversely, all genotypes isolated were in agreement with the most common genotypes detected in the European population [6,58]. …”

Studies of human polyomaviruses, with HPyV7, BKPyV, and JCPyV present in urine of allogeneic hematopoietic stem cell transplanted patients with or without hemorrhagic cystitis

“…Of note, 1 HC patient exhibited the presence of only JCPyV (genotype 1A) in the urine in a series of samples suggesting JCPyV as the causative agent of HC, consistent with the fact that JCPyV occasionally is found to contribute to HC . Moreover, in one of those studies JCPyV was of genotype 1A when occurring together with BKPyV in the urine, but of genotype 1B when present alone .…”