Cytomegalovirus in colorectal cancer and idiopathic ulcerative colitis

Mariguela, Viviane Casagrande; Chachá, Silvana Gama Florêncio; Cunha, Aldo de Albuquerque; Troncon, Luiz Ernesto de Almeida; Zucoloto, Sérgio; Figueiredo, Luíz Tadeu Moraes

doi:10.1590/s0036-46652008000200004

Cited by 22 publications

(23 citation statements)

References 16 publications

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“…However, taken along with other studies finding a deleterious impact of mCMV on colitis [9, 11, 13-17, 19-21, 28], we suggest that although small, the changes we detected may be meaningful, and set the stage for future studies into underlying mechanisms, in particular the aspect of enhanced bleeding. Another potentially important consideration in designing future studies is addressing the possible link between steroid-resistant UC and HCMV.…”

Section: Discussionsupporting

confidence: 74%

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

Becker

Stokes

2015

Pathophysiology

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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 versus 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 6 wk 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.

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Section: Discussionsupporting

confidence: 74%

“…However, the link between HCMV and UC is stronger [13-18]. The virus is prevalent in tissues of these patients [19] and reactivation of the virus in UC patients is associated with steroid-resistance during treatment [16]. The exact role of CMV in IBD is unknown.…”

Section: Introductionmentioning

confidence: 99%

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

Becker

Stokes

2015

Pathophysiology

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“…CMV DNA (34,37,38) or CMV antigens (34, 39) have been detected in colon tumors and in cell lines derived from them, but this association has not been universally confirmed (40)(41)(42)(43)(44)(45)(46), perhaps due to the different sensitivities of the methods used for detection of CMV in the different studies (41,43,47,48). Several reports have shown that CMV infection may interfere with key cellular signaling pathways, leading to enhanced survival and angiogenesis, and that it may also alter cell motility and adhesion (49).…”

Section: Figurementioning

confidence: 99%

The cytomegalovirus-encoded chemokine receptor US28 promotes intestinal neoplasia in transgenic mice

Bongers¹,

Maussang²,

Muniz³

et al. 2010

J. Clin. Invest.

102

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US28 is a constitutively active chemokine receptor encoded by CMV (also referred to as human herpesvirus 5), a highly prevalent human virus that infects a broad spectrum of cells, including intestinal epithelial cells (IECs). To study the role of US28 in vivo, we created transgenic mice (VS28 mice) in which US28 expression was targeted to IECs. Expression of US28 was detected in all IECs of the small and large intestine, including in cells expressing leucine rich repeat containing GPCR5 (Lgr5), a marker gene of intestinal epithelial stem cells. US28 expression in IECs inhibited glycogen synthase 3β (GSK-3β) function, promoted accumulation of β-catenin protein, and increased expression of Wnt target genes involved in the control of the cell proliferation. VS28 mice showed a hyperplastic intestinal epithelium and, strikingly, developed adenomas and adenocarcinomas by 40 weeks of age. When exposed to an inflammation-driven tumor model (azoxymethane/dextran sodium sulfate), VS28 mice developed a significantly higher tumor burden than control littermates. Transgenic coexpression of the US28 ligand CCL2 (an inflammatory chemokine) increased IEC proliferation as well as tumor burden, suggesting that the oncogenic activity of US28 can be modulated by inflammatory factors. Together, these results indicate that expression of US28 promotes development of intestinal dysplasia and cancer in transgenic mice and suggest that CMV infection may facilitate development of intestinal neoplasia in humans.

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“…Currently IHC is considered the gold standard for detecting CMV [7]. In fact, the prevalence of colonic CMV has been reported to be as high as 14-57% in patients with IBD who had IHC examination [8][9][10]. However, this is not routinely done in general practice.…”

mentioning

confidence: 99%