@article{2e5da021fa5144ab93dec9842c59e5e2,
title = "Virus-Plus-Susceptibility Gene Interaction Determines Crohn's Disease Gene Atg16L1 Phenotypes in Intestine",
abstract = "It is unclear why disease occurs in only a small proportion of persons carrying common risk alleles of disease susceptibility genes. Here we demonstrate that an interaction between a specific virus infection and a mutation in the Crohn's disease susceptibility gene Atg16L1 induces intestinal pathologies in mice. This virus-plus-susceptibility gene interaction generated abnormalities in granule packaging and unique patterns of gene expression in Paneth cells. Further, the response to injury induced by the toxic substance dextran sodium sulfate was fundamentally altered to include pathologies resembling aspects of Crohn's disease. These pathologies triggered by virus-plus-susceptibility gene interaction were dependent on TNFα and IFNγ and were prevented by treatment with broad spectrum antibiotics. Thus, we provide a specific example of how a virus-plus-susceptibility gene interaction can, in combination with additional environmental factors and commensal bacteria, determine the phenotype of hosts carrying common risk alleles for inflammatory disease. PaperClip:",
keywords = "Humdisease, Microbio, Molimmuno",
author = "Ken Cadwell and Patel, {Khushbu K.} and Maloney, {Nicole S.} and Liu, {Ta Chiang} and Ng, {Aylwin C.Y.} and Storer, {Chad E.} and Head, {Richard D.} and Ramnik Xavier and Stappenbeck, {Thaddeus S.} and Virgin, {Herbert W.}",
note = "Funding Information: This research was supported by grant U54 AI057160 Project 5 and the Broad Foundation (K.C., N.M., and H.W.V.), R01 AI084887 (T.S.S. and H.W.V.), the Lallage Feazel Wall Fellowship DRG-1972-08 from the Damon Runyon Cancer Research Foundation (K.C.), training grant NIH T32-AI007172 (N.M.), the Pew Foundation (K.K.P. and T.S.S.), Washington University Digestive Diseases Research Core Center DK52574, Pfizer biomedical agreement with Washington University, fellowship award from the Crohn's and Colitis Foundation of America (A.C.Y.N), and grants DK83756, DK086502, and DK043351 (R.J.X.). Washington University holds U.S. patents 7,041,444 B2, 7,264,923, and US 7,455,972 related to growth and detection of MNV. Washington University and H.W.V. receive income based on licenses for MNV technology. ",
year = "2010",
month = jun,
doi = "10.1016/j.cell.2010.05.009",
language = "English",
volume = "141",
pages = "1135--1145",
journal = "Cell",
issn = "0092-8674",
number = "7",
}