Viruses, autophagy genes, and Crohn's disease - PubMed (original) (raw)

Review

. 2011 Jul;3(7):1281-311.

doi: 10.3390/v3071281. Epub 2011 Jul 21.

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Review

Viruses, autophagy genes, and Crohn's disease

Vanessa M Hubbard et al. Viruses. 2011 Jul.

Abstract

The etiology of the intestinal disease Crohn's disease involves genetic factors as well as ill-defined environmental agents. Several genetic variants linked to this disease are associated with autophagy, a process that is critical for proper responses to viral infections. While a role for viruses in this disease remains speculative, accumulating evidence indicate that this possibility requires serious consideration. In this review, we will examine the three-way relationship between viruses, autophagy genes, and Crohn's disease and discuss how host-pathogen interactions can mediate complex inflammatory disorders.

Keywords: ATG16L1; Crohn’s disease; MNV; Paneth cells; autophagy; inflammatory bowel disease; intestine; mucosal immunity; norovirus.

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Figures

Figure 1

Figure 1

Overview of the three-way relationship discussed in this review. The relationship between autophagy and viruses (1) is the subject of this Special Issue of Viruses. The current evidence that viruses influence the course of Crohn’s disease (2) will be discussed in Section 2. Genes that participate in the autophagy pathway have been linked to Crohn’s disease (3) and will be discussed in Section 3. Finally, recent evidence in a mouse model linking all three (4) will be discussed in Section 4. The endoscopic image of the colon was taken from a Crohn’s disease patient and shows sigmoid pseudopolyps with cobblestone-like polyps.

Figure 2

Figure 2

Atg16L1 mutation leads to Paneth cell abnormalities during viral infection. The small intestinal crypt contains several Paneth cells with antimicrobial granules (red circles) and intestinal stem cells (green). The response to murine norovirus (MNV) infection leads to Paneth cell abnormalities specifically in Atg16L1 mutant mice including depletion of granules, aberrant morphology, and altered gene expression. In contrast, MNV does not cause these changes in control mice.

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