Open AccessEWI ‐2wint promotes CD 81 clustering that abrogates H epatitis C V irus entry
Author(s) -
Potel Julie,
Rassam Patrice,
Montpellier Claire,
Kaestner Laura,
Werkmeister Elisabeth,
Tews Birke A.,
Couturier Cyril,
Popescu CostinIoan,
Baumert Thomas F.,
Rubinstein Eric,
Dubuisson Jean,
Milhiet PierreEmmanuel,
Cocquerel Laurence
Publication year - 2013
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12112
Subject(s) - cd81 , tetraspanin , biology , hepatitis c virus , colocalization , context (archaeology) , virus , microbiology and biotechnology , virology , biochemistry , paleontology , cell
Summary CD 81 is a major receptor for H epatitis C V irus ( 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 CD 81 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 CD 81 molecules due to a decrease of the diffusion rate of mobile CD 81molecules and an increase in the proportion of confined molecules. Indeed, we demonstrated that EWI ‐2wint promotes CD 81 clustering and confinement in CD 81‐enriched areas. In addition, we showed that EWI ‐2wint influences the colocalization of CD 81 with C laudin‐1 – a co‐receptor required for HCV entry. Together, our results indicate that a change in membrane partitioning of CD 81 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 CD 81.