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JC Virus Infects the Enteric Glia of Patients with Chronic Idiopathic Intestinal Pseudo-obstruction
  1. Michael Selgrad (michael.selgrad{at}med.ovgu.de)
  1. Baylor University Medical Center, Dallas, TX, United States
    1. Roberto De Giorgio (deg{at}aosp.bo.it)
    1. University of Bologna, Italy
      1. Lucia Fini (luciaf{at}baylorhealth.edu)
      1. Baylor University Medical Center, Dallas, TX, United States
        1. Rosanna F. Cogliandro (deg{at}orsola-malpighi.med.unibo.it)
        1. University of Bologna, Italy
          1. Sharenda Williams (sharendw{at}baylorhealth.edu)
          1. Baylor University Medical Center, Dallas, TX, United States
            1. Vincenzo Stanghellini (vstang{at}med.unibo.it)
            1. University of Bologna, Italy
              1. Giovanni Barbara (gbarbara{at}med.unibo.it)
              1. St Orsola Hospital, Italy
                1. Marcello Tonini (tonini{at}unipv.it)
                1. University of Pavia, Italy
                  1. Roberto Corinaldesi (robecori{at}med.unibo.it)
                  1. University of Bologna, Italy
                    1. Robert M Genta (rgenta{at}mednet.swmed.edu)
                    1. University of Texas Southwestern Medical Center, VA North Texas Health Care System, Dallas, TX, United States
                      1. Rana Domiati-Saad (ranas{at}baylorhealth.edu)
                      1. Baylor University Medical Center, Dallas, TX, United States
                        1. Richard Meyer (richarme{at}baylorhealth.edu)
                        1. Baylor University Medical Center, Dallas, TX, United States
                          1. Ajay Goel (ajayg{at}baylorhealth.edu)
                          1. Baylor University Medical Center, Dallas, TX, United States
                            1. C Richard Boland (rickbo{at}baylorhealth.edu)
                            1. Baylor University Medical Center, Dallas, TX, United States
                              1. Luigi Ricciardiello (luigir{at}baylorhealth.edu)
                              1. Baylor University Medical Center, Dallas, TX, United States

                                Abstract

                                Background and aim: Chronic idiopathic intestinal pseudo-obstruction (CIIP) is characterized 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. We tested the hypothesis that JCV infects the myenteric plexuses of patients with CIIP.

                                Methods: We studied 10 patients with CIIP and 61 normal specimens (30 ascending colon and 31 ileum) from patients with uncomplicated colon cancer. 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 hybridization was performed for cellular localization of the JCV infection.

                                Results: Clinical studies demonstrated neurogenic impairment, and pathological analyses showed neuropathy in each CIIP patient. JCV TAg DNA was found in the myenteric plexuses of 8/10 (80%) of the 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-localized with GFAP expression, a marker of enteric glial cells.

                                Conclusion: JCV infection occurs in the myenteric plexuses of patients with CIIP. The JCV localization in enteroglial cells suggests a possible pathological role for this virus in enteric neuropathy.

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