Background and aim: Chronic idiopathic intestinal pseudo-obstruction (CIIP) is characterised by severe impairment of intestinal propulsive motility that mimics bowel obstruction. JC virus (JCV) is a polyomavirus that can infect brain glial cells causing a fatal disease, but may also be found throughout the normal gastrointestinal tract. The hypothesis that JCV infects the myenteric plexuses of patients with CIIP was tested.
Methods: 10 patients with CIIP and 61 normal specimens (30 ascending colon and 31 ileum) from patients with uncomplicated colon cancer were studied. DNA was extracted from the myenteric plexuses, and JCV T antigen (TAg) DNA and the viral regulatory region were detected by PCR and sequencing. Immunohistochemistry was performed to detect JCV viral protein expression, neuronal and glial markers. Fluorescence in situ hybridisation was performed for cellular localisation of the JCV infection.
Results: Clinical studies demonstrated neurogenic impairment, and pathological analyses showed neuropathy in each patient with CIIP. JCV TAg DNA was found in the myenteric plexuses of 8/10 (80%) of the patients with CIIP and 3/31 (9.7%) of the control patients (p<0.001). All samples were JCV Mad-1 strains. Seven of the 10 CIIP specimens expressed both JCV TAg and the JCV viral protein VP1, while none of the controls expressed either. JCV infection co-localised with glial fibrillary acidic protein expression, a marker of enteric glial cells.
Conclusion: JCV infection occurs in the myenteric plexuses of patients with CIIP. The JCV localisation in enteroglial cells suggests a possible pathological role for this virus in enteric neuropathy.
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Funding: This work was funded by: Grant R01 CA98572 from the National Cancer Institute of the NIH (to CRB), and funds from the Baylor Research Institute; by grants from the Italian Ministry of University, Research, Science and Technology (COFIN Projects number 2002068514_002, 2003064378_003, 2004062155_003) and RFO funds from the University of Bologna to VS, RDeG, GB and RC. RDeG is a recipient of a grant from the “Fondazione Del Monte di Bologna e Ravenna”.
Competing interests: None.
Ethics approval: Institutional Review Board approval was granted for this study from Baylor University Medical Center and from the University of Bologna.