The CD81 partner EWI-2wint inhibits hepatitis C virus entry.
Two to three percent of the world's population is chronically infected with hepatitis C virus (HCV) and thus at risk of developing liver cancer. Although precise mechanisms regulating HCV entry into hepatic cells are still unknown, several cell surface proteins have been identified as entry factors for this virus. Among these molecules, the tetraspanin CD81 is essential for HCV entry. Here, we have identified a partner of CD81, EWI-2wint, which is expressed in several cell lines but not in hepatocytes. Ectopic expression of EWI-2wint in a hepatoma cell line susceptible to HCV infection blocked viral entry by inhibiting the interaction between the HCV envelope glycoproteins and CD81. This finding suggests that, in addition to the presence of specific entry factors in the hepatocytes, the lack of a specific inhibitor can contribute to the hepatotropism of HCV. This is the first example of a pathogen gaining entry into host cells that lack a specific inhibitory factor.
Rocha-Perugini
Vera
V
Institut de Biologie de Lille (UMR8161), CNRS, Universités de Lille I et Lille II, Institut Pasteur de Lille, Lille, France.
Montpellier
Claire
C
Delgrange
David
D
Wychowski
Czeslaw
C
Helle
François
F
Pillez
André
A
Drobecq
Hervé
H
Le Naour
François
F
Charrin
Stéphanie
S
Levy
Shoshana
S
Rubinstein
Eric
E
Dubuisson
Jean
J
Cocquerel
Laurence
L
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000502:physiology; D016466:CHO Cells; D019556:COS Cells; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D006023:Glycoproteins / Q000737:chemistry; D016174:Hepacivirus / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000502:physiology; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D060225:Tetraspanin 28; D020298:U937 Cells
D015703:Antigens, CD; C554798:CD81 protein, human; D006023:Glycoproteins; C440028:IGSF8 protein, human; D008565:Membrane Proteins; D060225:Tetraspanin 28