The development of faithful in vitro replication systems for hepatitis C virus (HCV), reported by three separate groups last year, was hailed as one of the most important breakthroughs for hepatitis C research. Now, in a follow-up study, one group, led by Charles Rice from Rockefeller University in New York, USA, reports that their system generates viruses that are infectious not only in in vitro systems but also in vivo, in SCID mice and in the chimpanzee model of hepatitis C infection. These researchers created a chimeric hepatitis C genome (HCVcc strain FL-J6/JFH) by inserting five genes from an infectious clone of a genotype 2a HCV strain, HC-J6, into the subgenomic replicons of another 2a strain, JFH1. They show that the FL-J6/JFH strain is infectious in vivo and can persist in infected animals for several weeks, and that FL-J6/JFH grown in vivo could be isolated from infected animals and recultured in vitro. This system should allow researchers to investigate the molecular mechanisms of HCV pathogenesis; the challenge ahead is to develop equivalent systems for other HCV strains and serotypes in various cell types. PNAS
The precise cause of Crohn's disease, a chronic inflammatory disorder that mainly affects the intestines, remains enigmatic, although suspicion has been cast on infections with particular bacteria, such as mycobacteria, and on autoimmune processes. However, in a recent issue of The Lancet, Anthony Segall and colleagues suggest that the underlying defect in Crohn's disease is a generally weakened innate immune response. The authors found that Crohn's disease patients show reduced accumulation of neutrophils and interleukin-8 production at sites of trauma not only in the intestinal mucosa but also in the skin. This suggested the existence of a systemic defect, which was confirmed by in vitro analysis of macrophages from Crohn's disease patients. So, the authors hypothesize that Crohn's disease is a result of a failure of the innate immune response that delays or impairs the clearance of foreign material, such as bacteria, that breaches the mucosal barrier; this material can then be taken up by macrophages to form the granulomata characteristic of Crohn's disease. Although the defect is likely to be polygenic, Segall and colleagues suggest that vasodilatory drugs could be a possible new therapeutic avenue. Lancet
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