M.J. Evans, et al., "Claudin1 is a hepatitis C virus co-receptor required for a late step in entry," Nature, 446:801-5, 2007. (Cited in 81 papers)
In attempts to find out why hepatitis C virus (HCV) would not infect any cell type except liver, Matthew Evans at The Rockefeller University and colleagues expressed liver proteins in kidney cells and screened for HCV infection. The researchers found claudin-1, a tight junction protein which binds epithelial cells together at their sides, allowed the virus to infect a non-liver cell.
Current antiviral drugs that target some aspect of viral replication are usually not effective for very long; "viruses realize ways to sneak around" and resist the drug, says Evans. Blocking an entry protein, like claudin-1, on the host would strengthen any combination therapy for hepatitis C, a leading cause of liver failure.
The big picture:
The finding adds to a growing body of literature that implicates tight junction proteins in viral entry, says Alan Yu, a nephrologist at the University of Southern California Keck School of Medicine. The viruses essentially are a ligand for relaxing cellular tight junctions-a finding that could be useful in drug delivery technology, says Yu.
|claudin-1 inserted: Kidney cell infection increased 300 fold|
|claudin-1 silenced: Liver cell infection inhibited 50 fold|