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Epstein-Barr Virus Infection Is Common in Inflamed Gastrointestinal Mucosa

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Abstract

Background and Aims

Epstein-Barr virus (EBV) is present in the malignant epithelial cells of 10% of all gastric adenocarcinomas; however, localization of the virus in normal gastrointestinal mucosa is largely unexplored. In the present study, we measured EBV DNA and localized viral gene products in gastritis specimens (n = 89), normal gastric and colonic mucosa (n = 14), Crohn’s disease (n = 9), and ulcerative colitis (n = 11) tissues.

Methods

A battery of sensitive and specific quantitative polymerase chain reactions targeted six disparate regions of the EBV genome: BamH1 W, EBNA1, LMP1, LMP2, BZLF1, and EBER1. EBV infection was localized by EBV-encoded RNA (EBER) in situ hybridization and by immunohistochemical stains for viral latent proteins LMP1 and LMP2 and for viral lytic proteins BMRF1 and BZLF1. B lymphocytes were identified using CD20 immunostains.

Results

EBV DNA was essentially undetectable in normal gastric mucosa but was present in 46% of gastritis lesions, 44% of normal colonic mucosa, 55% of Crohn’s disease, and 64% of ulcerative colitis samples. Levels of EBV DNA exceeded what would be expected based on the numbers of B lymphocytes in inflamed tissues, suggesting that EBV is preferentially localized to inflammatory gastrointestinal lesions. Histochemical staining revealed EBER expression in lymphoid cells of some PCR-positive lesions. The viral lytic viral proteins, BMRF1 and BZLF1, were expressed in lymphoid cells of two ulcerative colitis tissues, both of which had relatively high viral loads by quantitative PCR.

Conclusion

EBV-infected lymphocytes are frequently present in inflamed gastric and colonic mucosa. Active viral replication in some lesions raises the possibility of virus-related perpetuation of gastrointestinal inflammation.

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Acknowledgments

The authors thank Sandra Elmore for technical assistance. This study was funded by the University of North Carolina Department of Pathology and Laboratory Medicine with support from the National Institutes of Health: Environmental Pathology Training Grant (T32-ES07017) supporting graduate studies of Julie L. Ryan, PhD, MPH, Cancer Epidemiology Award (K07CA125588) and funds for the UNC Center for Gastrointestinal Biology and Disease (P30 DK 034987) supporting Douglas R. Morgan, MD MPH, and the Alliance for Clinical Trials in Oncology (U10 CA031946), Clinical Translational Science Award (U54 RR024383), and Innovative Technologies for Molecular Analysis of Cancer (R21 CA155543) award supporting Margaret L. Gulley, MD.

Conflict of interest

MLG is a consultant for McKesson, Abbott Laboratories, and Roche Molecular Systems, and serves on the clinical advisory board of Generation Health.

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Authors and Affiliations

  1. Department of Dermatology and Radiation Oncology, University of Rochester Medical Center, 601 Elmwood Ave, Box 697, Rochester, NY, 14642-8704, USA

    Julie L. Ryan

  2. Sentara Virginia Beach General Hospital, 1060 First Colonial Rd, Virginia Beach, VA, 23454, USA

    You-Jun Shen

  3. Gastroenterology and Hepatology Division, Department of Medicine, University of North Carolina, Chapel Hill, NC, 27599-7555, USA

    Douglas R. Morgan

  4. Department of Pathology and Laboratory Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, 913 Brinkhous-Bullitt Building, Chapel Hill, NC, 27599-7525, USA

    Leigh B. Thorne & Margaret L. Gulley

  5. Departments of Medicine and Oncology, University of Wisconsin, Rm 611 Mcardle Cancer Research Building, 1400 University Avenue, Madison, WI, 53706, USA

    Shannon C. Kenney

  6. Department of Gastroenterology, Western Regional Hospital, Santa Rosa de Copan, Honduras

    Ricardo L. Dominguez

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  1. Julie L. Ryan
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  2. You-Jun Shen
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  3. Douglas R. Morgan
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  4. Leigh B. Thorne
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  6. Ricardo L. Dominguez
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  7. Margaret L. Gulley
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Correspondence to Margaret L. Gulley.

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Ryan, J.L., Shen, YJ., Morgan, D.R. et al. Epstein-Barr Virus Infection Is Common in Inflamed Gastrointestinal Mucosa. Dig Dis Sci 57, 1887–1898 (2012). https://doi.org/10.1007/s10620-012-2116-5

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  • DOI: https://doi.org/10.1007/s10620-012-2116-5

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