Tight junction proteins claudin-1 and occludin control hepatitis C virus entry and are downregulated during infection to prevent superinfection.
A tight junction (TJ) protein, claudin-1 (CLDN1), was identified recently as a key factor for hepatitis C virus (HCV) entry. Here, we show that another TJ protein, occludin, is also required for HCV entry. Mutational study of CLDN1 revealed that its tight junctional distribution plays an important role in mediating viral entry. Together, these data support the model in which HCV enters liver cells from the TJ. Interestingly, HCV infection of Huh-7 hepatoma cells downregulated the expression of CLDN1 and occludin, preventing superinfection. The altered TJ protein expression may contribute to the morphological and functional changes observed in HCV-infected hepatocytes.
Liu
Shufeng
S
Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pennsylvania, USA.
Yang
Wei
W
Shen
Le
L
Turner
Jerrold R
JR
Coyne
Carolyn B
CB
Wang
Tianyi
T
D045744:Cell Line, Tumor; D062445:Claudin-1; D015536:Down-Regulation; D016174:Hepacivirus / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D062793:Occludin; D019108:Tight Junctions / Q000821:virology*; D053586:Virus Internalization
C568108:CLDN1 protein, human; D062445:Claudin-1; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin