Isolate-dependent use of Claudin family members in cell entry by hepatitis C virus

HCV entry is a complex process involving many cellular receptor proteins such as CD81, scavenger receptor (SR-BI), Occludin (OCLN) and at least one member of the Claudin (CLDN) family. We investigated the role of the different CLDN proteins during HCV entry by using either HuH6 cells which lack endogenous CLDN1 expression but express CLDN6, or by using Huh-7.5 cells. Due to low endogenous CLDN1 expression, HuH6 cells were not susceptible to HCV genotype (GT) 2a infection. However, these cells were nevertheless permissive to HCV GT1, GT3 and GT6 entry indicating that some HCV isolates are restricted to use a spec…