Infection of intestinal epithelial cells and development of systemic disease following gastric instillation of murine gammaherpesvirus-68.
Murine gammaherpesvirus-68 (gammaHV-68) induces a lymphocytosis in mice and establishes a latent infection of B lymphocytes following intranasal administration in anaesthetized animals. Because gammaHV-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 gammaHV-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 gammaHV-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, gammaHV-68 given intragastrically resulted in lytic virus, viral RNA and viral DNA being present in isolated intestinal epithelial cells. Furthermore, gammaHV-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 gammaHV-68 can survive passage through the gastrointestinal tract and infect intestinal epithelial cells. Following infection of gut epithelial cells, gammaHV-68 can disseminate from mucosal sites to induce a systemic lymphocytosis which is similar to the disease induced following intranasal inoculation.
Peacock
J W
JW
Department of Biology, University of North Carolina at Charlotte, 9201 University City Blvd, Charlotte, NC 28223, USA. klbost@email.uncc.edu
Bost
K L
KL
D000284:Administration, Oral; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D004847:Epithelial Cells / Q000821:virology; D018142:Gammaherpesvirinae / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D006566:Herpesviridae Infections / Q000209:etiology* / Q000821:virology; D006801:Humans; D007422:Intestines / Q000821:virology; D008218:Lymphocytosis / Q000209:etiology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D013154:Spleen / Q000821:virology; D013270:Stomach; D013997:Time Factors
D017931:DNA Primers; D004279:DNA, Viral; D012367:RNA, Viral