The Neutralizing Face of Hepatitis C virus E2 envelope Glycoprotein

被引:54
作者
Tzarum, Netanel [1 ]
Wilson, Ian A. [1 ,2 ]
Law, Mansun [3 ]
机构
[1] Scripps Res Inst, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
[3] Scripps Res Inst, Dept Immunol & Microbiol, La Jolla, CA 92037 USA
来源
FRONTIERS IN IMMUNOLOGY | 2018年 / 9卷
关键词
hepatitis C virus; neutralizing antibodies; crystal structure; neutralizing face; vaccine design; HUMAN MONOCLONAL-ANTIBODY; STRUCTURAL BASIS; MEDIATED NEUTRALIZATION; HYPERVARIABLE REGION; E1; GLYCOPROTEIN; AMINO-TERMINUS; EPITOPE; AP33; INFECTION; PROTEIN;
D O I
10.3389/fimmu.2018.01315
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The high genetic variability of hepatitis C virus, together with the high level of glycosylation on the viral envelope proteins shielding potential neutralizing epitopes, pose a difficult challenge for vaccine development. An effective hepatitis C virus (HCV) vaccine must target conserved epitopes and the HCV E2 glycoprotein is the main target for such neutralizing antibodies (NAbs). Recent structural investigations highlight the presence of a highly conserved and accessible surface on E2 that is devoid of N-linked glycans and known as the E2 neutralizing face. This face is defined as a hydrophobic surface comprising the front layer (FL) and the CD81 binding loop (CD81bl) that overlap with the CD81 receptor binding site on E2. The neutralizing face consists of highly conserved residues for recognition by cross-NAbs, yet it appears to be high conformationally flexible, thereby presenting a moving target for NAbs. Three main overlapping neutralizing sites have been identified in the neutralizing face: antigenic site 412 (AS412), antigenic site 434 (AS434), and antigenic region 3 (AR3). Here, we review the structural analyses of these neutralizing sites, either as recombinant E2 or epitope-derived linear peptides in complex with bNAbs, to understand the functional and preferred conformations for neutralization, and for viral escape. Collectively, these studies provide a foundation and molecular templates to facilitate structure-based approaches for HCV vaccine development.
引用
收藏
页数:8
相关论文
共 50 条
  • [21] The dynamic properties of the Hepatitis C Virus E2 envelope protein unraveled by molecular dynamics
    Barone, Daniela
    Balasco, Nicole
    Autiero, Ida
    Vitagliano, Luigi
    JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2017, 35 (04) : 805 - 816
  • [22] Isolation of Human Monoclonal Antibodies to the Envelope E2 Protein of Hepatitis C Virus and Their Characterization
    Shimizu, Yohko K.
    Hijikata, Minako
    Oshima, Masamichi
    Shimizu, Kazufumi
    Alter, Harvey J.
    Purcell, Robert H.
    Yoshikura, Hiroshi
    Hotta, Hak
    PLOS ONE, 2013, 8 (02):
  • [23] Identification of glycosaminoglycan-binding sites within hepatitis C virus envelope glycoprotein E2
    Olenina, LV
    Kuzmina, TI
    Sobolev, BN
    Kuraeva, TE
    Kolesanova, EF
    Archakov, AI
    JOURNAL OF VIRAL HEPATITIS, 2005, 12 (06) : 584 - 593
  • [24] Immunization with a synthetic consensus hepatitis C virus E2 glycoprotein ectodomain elicits virus-neutralizing antibodies
    Tarr, Alexander W.
    Backx, Matthijs
    Hamed, Mohamed R.
    Urbanowicz, Richard A.
    McClure, C. Patrick
    Brown, Richard J. P.
    Ball, Jonathan K.
    ANTIVIRAL RESEARCH, 2018, 160 : 25 - 37
  • [25] A systematic analysis of a broadly neutralizing antibody AR3C epitopes on Hepatitis C virus E2 envelope glycoprotein and their cross-reactivity
    Sun, Jing
    Brusic, Vladimir
    BMC MEDICAL GENOMICS, 2015, 8
  • [26] Role of Hepatitis C Virus Envelope Glycoprotein E1 in Virus Entry and Assembly
    Tong, Yimin
    Lavillette, Dimitri
    Li, Qingchao
    Zhong, Jin
    FRONTIERS IN IMMUNOLOGY, 2018, 9
  • [27] Expression and structural properties of a chimeric protein based on the ectodomains of E1 and E2 hepatitis C virus envelope glycoproteins
    Tello, Daniel
    Rodriguez-Rodriguez, Mar
    Yelamos, Belen
    Gomez-Gutierrez, Julian
    Ortega, Sara
    Pacheco, Beatriz
    Peterson, Darrell L.
    Gavilanes, Francisco
    PROTEIN EXPRESSION AND PURIFICATION, 2010, 71 (02) : 123 - 131
  • [28] Immunoglobulin mimicry by hepatitis C virus envelope protein E2
    Hu, YW
    Rocheleau, L
    Larke, B
    Chui, L
    Lee, B
    Ma, M
    Liu, S
    Omlin, T
    Pelchat, M
    Brown, EG
    VIROLOGY, 2005, 332 (02) : 538 - 549
  • [29] Anti-hepatitis C virus E2 (HCV/E2) glycoprotein monoclonal antibodies and neutralization interference
    Sautto, Giuseppe
    Mancini, Nicasio
    Diotti, Roberta A.
    Solforosi, Laura
    Clementi, Massimo
    Burioni, Roberto
    ANTIVIRAL RESEARCH, 2012, 96 (01) : 82 - 89
  • [30] Structural and Antigenic Definition of Hepatitis C Virus E2 Glycoprotein Epitopes Targeted by Monoclonal Antibodies
    Sautto, Giuseppe
    Tarr, Alexander W.
    Mancini, Nicasio
    Clementi, Andmassimo
    CLINICAL & DEVELOPMENTAL IMMUNOLOGY, 2013,