55, P = 0007) Similarly, there was a significant correlation be

55, P = 0.007). Similarly, there was a significant correlation between the levels of claudin

and occludin and the slope of HCV-RNA increase during the first week after LT (r = 0.63, P = 0.005). Occludin and claudin-1 levels increased significantly 12 months after LT (P = 0.03 and P = 0.007, respectively). The expression pattern of both proteins, however, remained unchanged, colocalizing strongly (60%-94%) at the apical membrane of hepatocytes. Conclusions. HCV receptor levels at the time of LT seem to modulate early HCV kinetics. Hepatitis C recurrence after LT was associated with increased levels of claudin-1 and occludin in the hepatocyte cell membrane, although it did not alter http://www.selleckchem.com/products/torin-1.html their localization within the tight junctions. (HEPATOLOGY 2011;.) Hepatitis C virus (HCV) is the leading cause of chronic liver disease

in many regions of the world. Chronic hepatitis C progresses to cirrhosis and endstage liver failure in a significant proportion of patients over the years and is the main indication for liver transplantation (LT) in the Western world and Japan.1 Major advances have been achieved in the last few years towards a better understanding of the HCV life cycle. The development of a retroviral pseudoparticle system (HCVpp)2 and the ability of an HCV strain (JFH-1)3 to replicate and Gamma-secretase inhibitor release infectious particles in cell culture have been very relevant to the study of HCV entry into hepatocytes. Virus entry is commonly a complex event that requires sequential interactions

between viral surface proteins and cellular factors.4-10 The exact mechanisms by which HCV reaches the cytoplasm of liver cells and initiates replication are not yet completely understood. The fact that HCV needs several receptors with different membrane distributions favors the hypothesis of a coordinated entry process, such as what occurs with other viruses (i.e., Coxackie virus B).7, 10, 11 Ploss et al.10 recently proposed that HCV may initially interact with the luminal (sinusoidal) surface of the hepatocyte by contact with scavenger receptor B1 (SR-B1) and CD81. Thereafter a virus-receptor this website complex might migrate to the biliary pole (apical membrane), where the virus-receptor complex reaches the tight junctions and uptake into the cytoplasm would occur. The recent discovery that the tight junction proteins claudin-1 and occludin are essential factors for HCV entry into cells suggests a role for these proteins in HCV cell-cell transmission, a route of spread that is still under investigation.7 Recent studies have analyzed the potential role of HCV infection in the regulation of its putative receptors, particularly those located in the tight junctions. In one study, HCV infection appeared to down-regulate claudin-1 and occludin in Huh7 cells.

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