The impact of primary and persistent cytomegalovirus infection on the progression of acute colitis in a murine model.

Cytomegalovirus (CMV) infects 60-100% of the population worldwide. CMV has been implicated in many diseases through the induction of inflammation. Inflammatory bowel disease (IBD) affects over 1 million Americans annually. IBD, in particular ulcerative colitis, has been associated with CMV infection. Here we use a murine model to test if both primary and persistent CMV infections exacerbate colitis. C57Bl/6J mice were injected with Mock inoculum or murine CMV (mCMV) 4d (primary infection) or 6wks (persistent infection) before inducing colitis. Colitis was induced by administering 3% DSS (dextran sodium sulfate) in the drinking water for 6 days. Distilled water was given to controls. Disease activity index (DAI), derived from scores for stool consistency, body weight loss, occult blood, and rectal bleeding, was recorded daily. DAI increased early with DSS treatment in Mocks when compared with water-treated controls. This was accelerated by both primary and persistent mCMV and appeared to be primarily due to the earlier appearance of gross bleeding vs. their Mock controls. Mocks reached similar DAI values by day 6. Myeloperoxidase was modestly elevated in the mCMV 4d-DSS over the Mock 4d-DSS, however there was no such synergism in the 6wk groups. Histology was comparable in Mock and mCMV groups. Taken together our findings show that mCMV accelerated the development of acute colitis although a milder model of colitis may be needed to better delineate the impact of the virus on disease progression. Further work focusing on disruption of barrier function and bleeding may help determine the underlying mechanisms.