scholarly journals Coexpression of hepatitis C virus envelope proteins E1 and E2 in cis improves the stability of membrane insertion of E2

2001 ◽  
Vol 82 (7) ◽  
pp. 1629-1635 ◽  
Author(s):  
Laurence Cocquerel ◽  
Jean-Christophe Meunier ◽  
Anne Op de Beeck ◽  
Dorine Bonte ◽  
Czeslaw Wychowski ◽  
...  

The hepatitis C virus (HCV) genome encodes two envelope glycoproteins, E1 and E2. These proteins contain a large N-terminal ectodomain, and are anchored into membranes by their C-terminal transmembrane domain (TMD). The TMDs of HCV envelope proteins are multifunctional. In addition to their role as membrane anchors, they possess a signal sequence function in their C-terminal half, and play a major role in subcellular localization and assembly of these envelope proteins. In this work, the expression of full-length E2 led to secretion of a proportion of this protein, which is likely to be due to inefficient membrane insertion of a fraction of E2 expressed alone. However, when E1 and E2 were coexpressed from the same polyprotein, E2 was not secreted and remained tightly associated with membranes, suggesting that an early interaction between the TMDs of HCV envelope proteins improves the stability of membrane insertion of E2. These results reinforce the hypothesis that the TMDs of E1 and E2 are major factors in the assembly of the HCV envelope glycoprotein complex.

2000 ◽  
Vol 74 (8) ◽  
pp. 3623-3633 ◽  
Author(s):  
Laurence Cocquerel ◽  
Czeslaw Wychowski ◽  
Frederic Minner ◽  
François Penin ◽  
Jean Dubuisson

ABSTRACT For most membrane proteins, the transmembrane domain (TMD) is more than just an anchor to the membrane. The TMDs of hepatitis C virus (HCV) envelope proteins E1 and E2 are extreme examples of the multifunctionality of such membrane-spanning sequences. Indeed, they possess a signal sequence function in their C-terminal half, play a major role in endoplasmic reticulum localization of E1 and E2, and are potentially involved in the assembly of these envelope proteins. These multiple functions are supposed to be essential for the formation of the viral envelope. As for the other viruses of the familyFlaviviridae, these anchor domains are composed of two stretches of hydrophobic residues separated by a short segment containing at least one fully conserved charged residue. Replacement of these charged residues by an alanine in HCV envelope proteins led to an alteration of all of the functions performed by their TMDs, indicating that these functions are tightly linked together. These data suggest that the charged residues of the TMDs of HCV glycoproteins play a key role in the formation of the viral envelope.


2017 ◽  
Vol 13 (12) ◽  
pp. e1006735 ◽  
Author(s):  
Radhika Gopal ◽  
Kelli Jackson ◽  
Netanel Tzarum ◽  
Leopold Kong ◽  
Andrew Ettenger ◽  
...  

2006 ◽  
Vol 80 (4) ◽  
pp. 1817-1825 ◽  
Author(s):  
Mariko Kobayashi ◽  
Michael C. Bennett ◽  
Theodore Bercot ◽  
Ila R. Singh

ABSTRACT Hepatitis C virus (HCV) envelope proteins mediate the entry of virus into cells by binding to cellular receptors, resulting in fusion of the viral membrane with the host cell membrane and permitting the viral genome to enter the cytoplasm. We report the development of a robust and reproducible cell-cell fusion assay using envelope proteins from commonly occurring genotypes of HCV. The assay scored HCV envelope protein-mediated fusion by the production of fluorescent green syncytia and allowed us to elucidate many aspects of HCV fusion, including the pH of fusion, cell types that permit viral entry, and the conformation of envelope proteins essential for fusion. We found that fusion could be specifically inhibited by anti-HCV antibodies and by at least one peptide. We also generated a number of insertional mutations in the envelope proteins and tested nine of these using the fusion assay. We demonstrate that this fusion assay is a powerful tool for understanding the mechanism of HCV-mediated fusion, elucidating mutant function, and testing antiviral agents.


1999 ◽  
Vol 30 (2) ◽  
pp. 177-184 ◽  
Author(s):  
Andree Zibert ◽  
Wolfgang Kraas ◽  
R.Stefan Ross ◽  
Helga Meisel ◽  
Sabine Lechner ◽  
...  

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Katarzyna Grzyb ◽  
Anna Czarnota ◽  
Agnieszka Brzozowska ◽  
Anna Cieślik ◽  
Łukasz Rąbalski ◽  
...  

Biochimie ◽  
2003 ◽  
Vol 85 (3-4) ◽  
pp. 295-301 ◽  
Author(s):  
Anne Goffard ◽  
Jean Dubuisson

FEBS Journal ◽  
2014 ◽  
Vol 281 (11) ◽  
pp. 2558-2569 ◽  
Author(s):  
Daniel Tello ◽  
Mar Rodríguez-Rodríguez ◽  
Sara Ortega ◽  
Laura Lombana ◽  
Belén Yélamos ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document