Bruce D. Gelb
Mount Sinai School of Medicine, New York, New York, USA.
Phone: 212.241.3302; Fax: 212.241.3310; E-mail: firstname.lastname@example.org.
View this article at: http://www.jci.org/articles/view/46399?key=b94279a9b368432e4ab3
VIROLOGY: The genetic variant that increases the severity of hepatitis A virusinduced disease is
Infection with hepatitis A virus usually results in asymptomatic infection or mild disease. However, in a small subset of patients it can lead to severe disease and even liver failure. A team of researchers, led by Dale Umetsu, at Children's Hospital, Harvard Medical School, Boston, and Sergio Rosenzweig, at Hospital Nacional de Pediatra J. P. Garrahan, Argentina, have now identified a form of the TIM1 gene (which generates the protein to which hepatitis A virus binds as it enters cells) that is associated with severe hepatitis A virusinduced liver disease. Surprisingly, this form of the gene has previously been associated with protection against asthma and allergic diseases. The authors therefore suggest that infection with hepatitis A virus has driven the natural selection of forms of the TIM-1 protein that bind hepatitis A virus less efficiently, thereby protecting against severe hepatitis A virusinduced disease, but which may predispose toward inflammation associated with asthma and allergy.
In an accompanying commentary, Lucienne Chatenoud and Jean-Franois Bach, at Hpital Necker Enfants Malades, France, discuss the importance of this paper and highlight the novel concepts it introduces.
TITLE: A polymorphism in TIM1 is associated with susceptibility to severe hepatitis A virus infection in humans
Dale T. Umetsu
|Contact: Ushma Neill|
Journal of Clinical Investigation