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Journal of General Virology (2000), 81, 421-429.
© 2000 Society for General Microbiology


Animal: DNA Viruses

Infection of intestinal epithelial cells and development of systemic disease following gastric instillation of murine gammaherpesvirus-68

James W. Peacock1 and Kenneth L. Bost1

Department of Biology, University of North Carolina at Charlotte, 9201 University City Blvd, Charlotte, NC 28223, USA1

Author for correspondence: Kenneth Bost. Fax +1 704 547 3128. e-mail klbost{at}email.uncc.edu

Murine gammaherpesvirus-68 ({gamma}HV-68) induces a lymphocytosis in mice and establishes a latent infection of B lymphocytes following intranasal administration in anaesthetized animals. Because {gamma}HV-68 is a gammaherpesvirus, it has been used as a model to understand the pathogenesis of Epstein–Barr virus (EBV) and human herpesvirus-8 (HHV-8) infections. In this study, we investigated the unlikely possibility that {gamma}HV-68 could survive the harsh gastrointestinal environment to efficiently infect intestinal epithelial cells, and then disseminate from mucosal sites to cause systemic disease. Surprisingly, oral administration, or gastric instillation which by-passed the oral cavity, readily caused a systemic lymphocytosis and established a latent infection in splenic leukocytes. The finding that {gamma}HV-68 could readily infect adult mice following gastric instillation strongly suggested that intestinal epithelial cells could be productively infected. Unlike the more routinely used method of intranasal inoculation, {gamma}HV-68 given intragastrically resulted in lytic virus, viral RNA and viral DNA being present in isolated intestinal epithelial cells. Furthermore, {gamma}HV-68 RNA and DNA, but not latent virus, could be detected in epithelial cells as long as 30 days post-infection, suggesting that some of these cells might be persistently infected. Taken together, these studies demonstrate that {gamma}HV-68 can survive passage through the gastrointestinal tract and infect intestinal epithelial cells. Following infection of gut epithelial cells, {gamma}HV-68 can disseminate from mucosal sites to induce a systemic lymphocytosis which is similar to the disease induced following intranasal inoculation.




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