Crohn's disease: the case for measles virus.

Crohn's disease has the epidemiological and pathological hallmarks of an infection with a long natural history. Its emergence in developed countries in the middle of the 20th Century represents an instant in the continuum of human evolution, indicating either a new infection or, as with poliomyelitis, a changing pattern of exposure to a common childhood pathogen. Both short- and long-term outcomes from viral infection are largely dependent upon age and dose of exposure. We and others have suggested that measles virus may be causally related to Crohn's disease, and that the associated risk is an atypical pattern of exposure. Early, intensive, and concurrent infections have been identified as risks for subacute sclerosing panencephalitis, a delayed sequelae to measles virus infection, possibly through a process of high zone immunological tolerance and persistent infection. The data for Crohn's disease suggest that persistent infection may follow early low dose exposure and low zone immunological tolerance. The changing pattern of measles virus exposure this century would be consistent with a shift towards lower dose of infection. Such an exposure would also be consistent with persistence of the virus at very low copy number within discrete foci of granulomatous inflammation. The ability of measles virus to profoundly disrupt mucosal immune responses may provide the human counterpart of the cytokine-gene knockout.