Claudin association with CD81 defines hepatitis C virus entry

Area of Science:

• Virology
• Cell Biology
• Hepatology

Background:

• Hepatitis C virus (HCV) entry into host cells is a complex process.
• Key receptors include CD81, scavenger receptor class B member I, Claudin-1, and Occludin.
• The precise role of Claudin-1 in HCV internalization remains unclear.

Purpose of the Study:

• To investigate the relationship between Claudin-1, CD81, and HCV entry.
• To determine the functional significance of Claudin-1 and CD81 interactions in HCV infection.

Main Methods:

• Fluorescence resonance energy transfer (FRET) and stoichiometric imaging.
• Site-directed mutagenesis of Claudin-1 and Claudin-7.
• Analysis of HCV receptor activity and viral entry in polarized HepG2 cells.

Main Results:

• Claudin-1 actively associates with CD81 at the plasma membrane.
• Mutations in Claudin-1's extracellular loop disrupt CD81 binding and HCV entry.
• Modifying Claudin-7 with these mutations confers CD81 complex formation and permits HCV entry.
• Claudin-1 and CD81 form complexes at the basolateral membrane, not the tight junction.

Conclusions:

• Claudin-CD81 complexes are essential for Hepatitis C virus infection.
• These complexes are localized to the basolateral surface of polarized liver cells, consistent with HCV entry routes.
• The interaction between Claudin-1 and CD81 is a critical determinant of HCV cellular entry.