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

Prix Suzanne Tassier (10e période biennale, 1975-1976). Rapport du Jury

Harsin Paul, Montpellier Gérard de, Préaux Claire. Prix Suzanne Tassier (10e période biennale, 1975-1976). Rapport du Jury. In: Bulletin de la Classe des lettres et des sciences morales et politiques, tome 63, 1977. p. 90

Hepatitis E Virus (HEV) Open Reading Frame 2 Antigen Kinetics in Human-Liver Chimeric Mice and Its Impact on HEV Diagnosis

International audienceBackground: Hepatitis E virus infection (HEV) is an emerging problem in developed countries. Diagnosis of HEV infection is based on the detection of HEV-specific antibodies, viral RNA and/or antigens (Ag). Humanized mice were previously reported as a model for the study of HEV infection, but published data was focused on the quantification of viral RNA. However, the kinetics of HEV Ag expression during the course of infection remains poorly understood.Methods: Plasma and fecal suspensions from HEV infected and ribavirin-treated humanized mice were analyzed using HEV antigen ELISA, RT-qPCR, density gradient and Western blotting.Result: ORF2 Ag was detected in both plasma and stool of HEV infected mice, and increased overtime. Contrary to HEV RNA, ORF2 Ag levels were higher in mouse plasma than in stool. Interestingly, ORF2 was detected in plasma of mice that were RNA negative in plasma but RNA positive in stool; and after viral clearance by ribavirin. Plasma density gradient analysis revealed the presence of the non-infectious glycosylated form of ORF2.Conclusion: ORF2 Ag can be used as a marker of active HEV infection and the assessment of antiviral therapy, especially when fecal samples are not available or molecular diagnostic tests are not accessible

Contribution of the charged residues of hepatitis C virus glycoprotein E2 transmembrane domain to the functions of the E1E2 heterodimer.

The envelope glycoproteins of Hepatitis C virus (HCV), E1 and E2, form a heterodimer that is retained in the endoplasmic reticulum (ER). The transmembrane (TM) domains play a major role in E1E2 heterodimerization and in ER retention. Two fully conserved charged residues in the middle of the TM domain of E2 (Asp and Arg) are crucial for these functions. Replacement of the Asp residue by a Leu impaired E1E2 heterodimerization, whereas the Arg-to-Leu mutation had a milder effect. Both Asp and Arg residues were shown to contribute to the ER retention function of E2. In addition, the entry function of HCV envelope glycoproteins was affected by these mutations. Together, these data indicate that the charged residues present in the TM domain of E2 play a major role in the biogenesis and the entry function of the E1E2 heterodimer. However, the Asp and Arg residues do not contribute equally to these functions.Journal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Rôles des résidus chargés du domaine transmembranaire de la glycoprotéine E2 du VHC dans les fonctions d'assemblage et d'entrée virale.

info:eu-repo/semantics/nonPublishe