EWI-2wint promotes CD81 clustering that abrogates Hepatitis C Virus entry

Cell Microbiol. 2013 Jul;15(7):1234-52. doi: 10.1111/cmi.12112. Epub 2013 Feb 16.


CD81 is a major receptor for Hepatitis C Virus (HCV). It belongs to the tetraspanin family whose members form dynamic clusters with numerous partner proteins and with one another, forming tetraspanin-enriched areas in the plasma membrane. In our study, we combined single-molecule microscopy and biochemistry experiments to investigate the clustering and membrane behaviour of CD81 in the context of cells expressing EWI-2wint, a natural inhibitor of HCV entry. Interestingly, we found that EWI-2wint reduces the global diffusion of CD81 molecules due to a decrease of the diffusion rate of mobile CD81 molecules and an increase in the proportion of confined molecules. Indeed, we demonstrated that EWI-2wint promotes CD81 clustering and confinement in CD81-enriched areas. In addition, we showed that EWI-2wint influences the colocalization of CD81 with Claudin-1 - a co-receptor required for HCV entry. Together, our results indicate that a change in membrane partitioning of CD81 occurs in the presence of EWI-2wint. This study gives new insights on the mechanism by which HCV enters into its target cells, namely by exploiting the dynamic properties of CD81.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism*
  • Cell Line
  • Hepacivirus / physiology*
  • Hepatocytes / virology
  • Host-Pathogen Interactions*
  • Humans
  • Membrane Proteins / metabolism*
  • Receptors, Virus / metabolism*
  • Tetraspanin 28 / metabolism*
  • Virus Internalization*


  • Antigens, CD
  • IGSF8 protein, human
  • Membrane Proteins
  • Receptors, Virus
  • Tetraspanin 28