Viruses, Autophagy Genes, and Crohn’s Disease 英文参考文献.docVIP

Viruses 2011, 3, 1281-1311; doi:10.3390/v3071281 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Viruses, Autophagy Genes, and Crohn’s Disease Vanessa M. Hubbard and Ken Cadwell * Skirball Institute of Biomolecular Medicine, Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA * Author to whom correspondence should be addressed; E-Mail: ken.cadwell@; Tel.: +1-212-263-8891; Fax: +1-212-263-5711. Received: 8 June 2011; in revised form: 12 July 2011 / Accepted: 13 July 2011 / Published: 21 July 2011 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: Crohn’s disease; inflammatory bowel disease; norovirus; MNV; ATG16L1; autophagy; mucosal immunity; intestine; Paneth cells 1. Introduction Crohn’s disease is a major form of inflammatory bowel disease that affects as many as 1 in 500 individuals [1]. Family and twin studies have demonstrated a strong heritable component to the disease that is the subject of intense research [2]. The age of onset is frequently in the second decade of life, and most patients progress to a relapsing disease characterized by abdominal pain, bloody diarrhea, vomiting, and weight loss. Crohn’s disease is distinguished from other types of inflammatory bowel disease such as ulcerative colitis in that the inflammation is often discontinuous, transmural, and can inv