Genetic and structural insights into broad neutralization of hepatitis C virus by human VH1-69 antibodies

Tzarum, Netanel; Giang, Erick; Kong, Leopold; He, Linling; Prentoe, Jannick; Augestad, Elias; Hua, Yuanzi; Castillo, Shaun; Lauer, Georg M.; Bukh, Jens; Zhu, Jiang; Wilson, Ian A.; Law, Mansun

doi:10.1126/sciadv.aav1882

Genetic and structural insights into broad neutralization of hepatitis C virus by human V_H1-69 antibodies

Journal Article · Tue Jan 01 23:00:00 EST 2019 · Science Advances

DOI:https://doi.org/10.1126/sciadv.aav1882· OSTI ID:1502256

Tzarum, Netanel ^[1]; Giang, Erick ^[2]; Kong, Leopold ^[2]; ^[2]; ^[3]; ^[3]; Hua, Yuanzi ^[2]; ^[2]; ^[4]; ^[3]; ^[2]; ^[2]; ^[2]

The Scripps Research Inst., La Jolla, CA (United States); DOE/OSTI
The Scripps Research Inst., La Jolla, CA (United States)
Univ. of Copenhagen (Denmark)
Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States)

An effective vaccine to the antigenically diverse hepatitis C virus (HCV) must target conserved immune epitopes. Here, we investigate cross-neutralization of HCV genotypes by broadly neutralizing antibodies (bNAbs) encoded by the relatively abundant human gene family V_H1-69. We have deciphered the molecular requirements for cross-neutralization by this unique class of human antibodies from crystal structures of HCV E2 in complex with bNAbs. An unusually high binding affinity is found for germ line–reverted versions of V_H1-69 precursor antibodies, and neutralization breadth is acquired during affinity maturation. Deep sequencing analysis of an HCV-immune B cell repertoire further demonstrates the importance of the V_H1-69 gene family in the generation of HCV bNAbs. This study therefore provides critical insights into immune recognition of HCV with important implications for rational vaccine design.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institute of Health (NIH)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1502256

Journal Information:: Science Advances, Journal Name: Science Advances Journal Issue: 1 Vol. 5; ISSN 2375-2548

Publisher:: AAASCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (73)

Characterization of host-range and cell entry properties of the major genotypes and subtypes of hepatitis C virus Lavillette, Dimitri; Tarr, Alexander W.; Voisset, C�cile Hepatology, Vol. 41, Issue 2 https://doi.org/10.1002/hep.20542	journal	January 2005
Development and characterization of hepatitis C virus genotype 1-7 cell culture systems: Role of CD81 and scavenger receptor class B type I and effect of antiviral drugs Gottwein, Judith M.; Scheel, Troels K. H.; Jensen, Tanja B. Hepatology, Vol. 49, Issue 2 https://doi.org/10.1002/hep.22673	journal	October 2008
Hypervariable region 1 shielding of hepatitis C virus is a main contributor to genotypic differences in neutralization sensitivity Prentoe, Jannick; Velázquez-Moctezuma, Rodrigo; Foung, Steven K. H. Hepatology, Vol. 64, Issue 6 https://doi.org/10.1002/hep.28705	journal	August 2016
Hepatitis C Virus: An Infectious Molecular Clone of a Second Major Genotype (2a) and Lack of Viability of Intertypic 1a and 2a Chimeras Yanagi, Masayuki; Purcell, Robert H.; Emerson, Suzanne U. Virology, Vol. 262, Issue 1 https://doi.org/10.1006/viro.1999.9889	journal	September 1999
Multidonor Analysis Reveals Structural Elements, Genetic Determinants, and Maturation Pathway for HIV-1 Neutralization by VRC01-Class Antibodies Zhou, Tongqing; Zhu, Jiang; Wu, Xueling Immunity, Vol. 39, Issue 2 https://doi.org/10.1016/j.immuni.2013.04.012	journal	August 2013
Key gp120 Glycans Pose Roadblocks to the Rapid Development of VRC01-Class Antibodies in an HIV-1-Infected Chinese Donor Kong, Leopold; Ju, Bin; Chen, Yajing Immunity, Vol. 44, Issue 4 https://doi.org/10.1016/j.immuni.2016.03.006	journal	April 2016
Naive B Cells with High-Avidity Germline-Encoded Antigen Receptors Produce Persistent IgM+ and Transient IgG+ Memory B Cells Pape, Kathryn A.; Maul, Robert W.; Dileepan, Thamotharampillai Immunity, Vol. 48, Issue 6 https://doi.org/10.1016/j.immuni.2018.04.019	journal	June 2018
Perspectives for the utilization of neutralizing human monoclonal antibodies as anti-HCV drugs Burioni, Roberto; Perotti, Mario; Mancini, Nicasio Journal of Hepatology, Vol. 49, Issue 2 https://doi.org/10.1016/j.jhep.2008.05.008	journal	August 2008
Inference of Macromolecular Assemblies from Crystalline State Krissinel, Evgeny; Henrick, Kim Journal of Molecular Biology, Vol. 372, Issue 3 https://doi.org/10.1016/j.jmb.2007.05.022	journal	September 2007
Glycosylation of hepatitis C virus envelope proteins Goffard, Anne; Dubuisson, Jean Biochimie, Vol. 85, Issue 3-4 https://doi.org/10.1016/s0300-9084(03)00004-x	journal	March 2003
LigPlot+: Multiple Ligand–Protein Interaction Diagrams for Drug Discovery Laskowski, Roman A.; Swindells, Mark B. Journal of Chemical Information and Modeling, Vol. 51, Issue 10 https://doi.org/10.1021/ci200227u	journal	October 2011
Hepatitis C Treatment and Barriers to Eradication Konerman, Monica A.; Lok, Anna S. F. Clinical and Translational Gastroenterology, Vol. 7, Issue 9 https://doi.org/10.1038/ctg.2016.50	journal	January 2016
Structure of the core ectodomain of the hepatitis C virus envelope glycoprotein 2 Khan, Abdul Ghafoor; Whidby, Jillian; Miller, Matthew T. Nature, Vol. 509, Issue 7500 https://doi.org/10.1038/nature13117	journal	February 2014
HCV transmission in industrialized countries and resource-constrained areas Thursz, Mark; Fontanet, Arnaud Nature Reviews Gastroenterology & Hepatology, Vol. 11, Issue 1 https://doi.org/10.1038/nrgastro.2013.179	journal	October 2013
Toward a more accurate view of human B-cell repertoire by next-generation sequencing, unbiased repertoire capture and single-molecule barcoding He, Linling; Sok, Devin; Azadnia, Parisa Scientific Reports, Vol. 4, Issue 1 https://doi.org/10.1038/srep06778	journal	October 2014
Designing Tomorrow's Vaccines Nabel, Gary J. New England Journal of Medicine, Vol. 368, Issue 6 https://doi.org/10.1056/nejmra1204186	journal	February 2013
Structural basis of tyrosine sulfation and VH-gene usage in antibodies that recognize the HIV type 1 coreceptor-binding site on gp120 Huang, C. -c.; Venturi, M.; Majeed, S. Proceedings of the National Academy of Sciences, Vol. 101, Issue 9 https://doi.org/10.1073/pnas.0308527100	journal	February 2004
Evidence for cross-genotype neutralization of hepatitis C virus pseudo-particles and enhancement of infectivity by apolipoprotein C1 Meunier, J. -C.; Engle, R. E.; Faulk, K. Proceedings of the National Academy of Sciences, Vol. 102, Issue 12 https://doi.org/10.1073/pnas.0501275102	journal	March 2005
Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus Giang, E.; Dorner, M.; Prentoe, J. C. Proceedings of the National Academy of Sciences, Vol. 109, Issue 16 https://doi.org/10.1073/pnas.1114927109	journal	April 2012
Mining the antibodyome for HIV-1-neutralizing antibodies with next-generation sequencing and phylogenetic pairing of heavy/light chains Zhu, J.; Ofek, G.; Yang, Y. Proceedings of the National Academy of Sciences, Vol. 110, Issue 16 https://doi.org/10.1073/pnas.1219320110	journal	March 2013
De novo identification of VRC01 class HIV-1-neutralizing antibodies by next-generation sequencing of B-cell transcripts Zhu, J.; Wu, X.; Zhang, B. Proceedings of the National Academy of Sciences, Vol. 110, Issue 43 https://doi.org/10.1073/pnas.1306262110	journal	October 2013
Genetic organization and diversity of the hepatitis C virus. Choo, Q. L.; Richman, K. H.; Han, J. H. Proceedings of the National Academy of Sciences, Vol. 88, Issue 6 https://doi.org/10.1073/pnas.88.6.2451	journal	March 1991
Experimental Infection of Chimpanzees with Hepatitis C Virus of Genotype 5a: Genetic Analysis of the Virus and Generation of a Standardized Challenge Pool Bukh, Jens; Apgar, Carl L.; Engle, Ronald The Journal of Infectious Diseases, Vol. 178, Issue 4 https://doi.org/10.1086/515683	journal	October 1998
Complete nucleotide sequence of a type 4 hepatitis C virus variant, the predominant genotype in the Middle East. Chamberlain, R. W.; Simmonds, P.; Adams, N. Journal of General Virology, Vol. 78, Issue 6 https://doi.org/10.1099/0022-1317-78-6-1341	journal	June 1997
PHENIX : building new software for automated crystallographic structure determination Adams, Paul D.; Grosse-Kunstleve, Ralf W.; Hung, Li-Wei Acta Crystallographica Section D Biological Crystallography, Vol. 58, Issue 11 https://doi.org/10.1107/s0907444902016657	journal	October 2002
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/s0907444904019158	journal	November 2004
Likelihood-enhanced fast translation functions McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Storoni, Laurent C. Acta Crystallographica Section D Biological Crystallography, Vol. 61, Issue 4 https://doi.org/10.1107/s0907444905001617	journal	March 2005
Antibody Recognition of a Highly Conserved Influenza Virus Epitope Ekiert, D. C.; Bhabha, G.; Elsliger, M. -A. Science, Vol. 324, Issue 5924 https://doi.org/10.1126/science.1171491	journal	April 2009
Transmission of Hepatitis C by Intrahepatic Inoculation with Transcribed RNA Kolykhalov, A. A. Science, Vol. 277, Issue 5325 https://doi.org/10.1126/science.277.5325.570	journal	July 1997
Replication of Subgenomic Hepatitis C Virus RNAs in a Hepatoma Cell Line Lohmann, V. Science, Vol. 285, Issue 5424 https://doi.org/10.1126/science.285.5424.110	journal	July 1999
Chronic Hepatitis C Virus Infection Breaks Tolerance and Drives Polyclonal Expansion of Autoreactive B Cells Roughan, Jill E.; Reardon, Kathryn M.; Cogburn, Kristin E. Clinical and Vaccine Immunology, Vol. 19, Issue 7 https://doi.org/10.1128/cvi.00194-12	journal	May 2012
Novel Infectious cDNA Clones of Hepatitis C Virus Genotype 3a (Strain S52) and 4a (Strain ED43): Genetic Analyses and In Vivo Pathogenesis Studies Gottwein, J. M.; Scheel, T. K. H.; Callendret, B. Journal of Virology, Vol. 84, Issue 10 https://doi.org/10.1128/jvi.02667-09	journal	March 2010
Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design Burton, Dennis R.; Hangartner, Lars Annual Review of Immunology, Vol. 34, Issue 1 https://doi.org/10.1146/annurev-immunol-041015-055515	journal	May 2016
V H 1-69 gene is preferentially used by hepatitis C virus–associated B cell lymphomas and by normal B cells responding to the E2 viral antigen Chan, Chunghuang Hubert; Hadlock, Kenneth G.; Foung, Steven K. H. Blood, Vol. 97, Issue 4 https://doi.org/10.1182/blood.v97.4.1023	journal	February 2001
Hepatitis C virus Broadly Neutralizing Monoclonal Antibodies Isolated 25 Years after Spontaneous Clearance Merat, Sabrina J.; Molenkamp, Richard; Wagner, Koen PLOS ONE, Vol. 11, Issue 10 https://doi.org/10.1371/journal.pone.0165047	journal	October 2016
Applying antibody-sensitive hypervariable region 1-deleted hepatitis C virus to the study of escape pathways of neutralizing human monoclonal antibody AR5A Velázquez-Moctezuma, Rodrigo; Law, Mansun; Bukh, Jens PLOS Pathogens, Vol. 13, Issue 2 https://doi.org/10.1371/journal.ppat.1006214	journal	February 2017
Probing the antigenicity of hepatitis C virus envelope glycoprotein complex by high-throughput mutagenesis Gopal, Radhika; Jackson, Kelli; Tzarum, Netanel PLOS Pathogens, Vol. 13, Issue 12 https://doi.org/10.1371/journal.ppat.1006735	journal	December 2017
Hidden Lineage Complexity of Glycan-Dependent HIV-1 Broadly Neutralizing Antibodies Uncovered by Digital Panning and Native-Like gp140 Trimer He, Linling; Lin, Xiaohe; de Val, Natalia Frontiers in Immunology, Vol. 8 https://doi.org/10.3389/fimmu.2017.01025	journal	August 2017
The Neutralizing Face of Hepatitis C Virus E2 Envelope Glycoprotein Tzarum, Netanel; Wilson, Ian A.; Law, Mansun Frontiers in Immunology, Vol. 9 https://doi.org/10.3389/fimmu.2018.01315	journal	June 2018
Somatic populations of PGT135–137 HIV-1-neutralizing antibodies identified by 454 pyrosequencing and bioinformatic Zhu, Jiang Frontiers in Microbiology, Vol. 3 https://doi.org/10.3389/fmicb.2012.00315	journal	January 2012
CD81 and Hepatitis C Virus (HCV) Infection Fénéant, Lucie; Levy, Shoshana; Cocquerel, Laurence Viruses, Vol. 6, Issue 2 https://doi.org/10.3390/v6020535	journal	February 2014
Accessing the Kabat antibody sequence database by computer: ACCESSING THE KABAT DATABASE BY COMPUTER Martin, Andrew C. R. Proteins: Structure, Function, and Bioinformatics, Vol. 25, Issue 1 https://doi.org/10.1002/(SICI)1097-0134(199605)25:1<130::AID-PROT11>3.0.CO;2-L	journal	May 1996
NMRPipe: A multidimensional spectral processing system based on UNIX pipes Delaglio, Frank; Grzesiek, Stephan; Vuister, GeertenW. Journal of Biomolecular NMR, Vol. 6, Issue 3 https://doi.org/10.1007/BF00197809	journal	November 1995
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains Lefranc, Marie-Paule; Pommié, Christelle; Ruiz, Manuel Developmental & Comparative Immunology, Vol. 27, Issue 1 https://doi.org/10.1016/S0145-305X(02)00039-3	journal	January 2003
Glycosylation of hepatitis C virus envelope proteins Goffard, Anne; Dubuisson, Jean Biochimie, Vol. 85, Issue 3-4 https://doi.org/10.1016/S0300-9084(03)00004-X	journal	March 2003
Antibody 27F3 Broadly Targets Influenza A Group 1 and 2 Hemagglutinins through a Further Variation in V H 1-69 Antibody Orientation on the HA Stem Lang, Shanshan; Xie, Jia; Zhu, Xueyong Cell Reports, Vol. 20, Issue 12 https://doi.org/10.1016/j.celrep.2017.08.084	journal	September 2017
From non-A, non-B hepatitis to hepatitis C virus cure Pawlotsky, Jean-Michel; Feld, Jordan J.; Zeuzem, Stefan Journal of Hepatology, Vol. 62, Issue 1 https://doi.org/10.1016/j.jhep.2015.02.006	journal	April 2015
Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals Conti, Fabio; Buonfiglioli, Federica; Scuteri, Alessandra Journal of Hepatology, Vol. 65, Issue 4 https://doi.org/10.1016/j.jhep.2016.06.015	journal	October 2016
Rapid development of broadly influenza neutralizing antibodies through redundant mutations Pappas, Leontios; Foglierini, Mathilde; Piccoli, Luca Nature, Vol. 516, Issue 7531 https://doi.org/10.1038/nature13764	journal	October 2014
Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge Law, Mansun; Maruyama, Toshiaki; Lewis, Jamie Nature Medicine, Vol. 14, Issue 1 https://doi.org/10.1038/nm1698	journal	December 2007
The ins and outs of hepatitis C virus entry and assembly Lindenbach, Brett D.; Rice, Charles M. Nature Reviews Microbiology, Vol. 11, Issue 10 https://doi.org/10.1038/nrmicro3098	journal	September 2013
Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses Sui, Jianhua; Hwang, William C.; Perez, Sandra Nature Structural & Molecular Biology, Vol. 16, Issue 3 https://doi.org/10.1038/nsmb.1566	journal	February 2009
Designing Tomorrow's Vaccines Nabel, Gary J. New England Journal of Medicine, Vol. 368, Issue 6 https://doi.org/10.1056/NEJMra1204186	journal	February 2013
Structural flexibility at a major conserved antibody target on hepatitis C virus E2 antigen Kong, Leopold; Lee, David E.; Kadam, Rameshwar U. Proceedings of the National Academy of Sciences, Vol. 113, Issue 45 https://doi.org/10.1073/pnas.1609780113	journal	October 2016
Challenge Pools of Hepatitis C Virus Genotypes 1–6 Prototype Strains: Replication Fitness and Pathogenicity in Chimpanzees and Human Liver–Chimeric Mouse Models Bukh, Jens; Meuleman, Philip; Tellier, Raymond The Journal of Infectious Diseases, Vol. 201, Issue 9 https://doi.org/10.1086/651579	journal	May 2010
MolProbity: all-atom contacts and structure validation for proteins and nucleic acids Davis, I. W.; Leaver-Fay, A.; Chen, V. B. Nucleic Acids Research, Vol. 35, Issue Web Server https://doi.org/10.1093/nar/gkm216	journal	May 2007
Proposed update to the taxonomy of the genera Hepacivirus and Pegivirus within the Flaviviridae family Smith, Donald B.; Becher, Paul; Bukh, Jens Journal of General Virology, Vol. 97, Issue 11 https://doi.org/10.1099/jgv.0.000612	journal	November 2016
PHENIX : building new software for automated crystallographic structure determination Adams, Paul D.; Grosse-Kunstleve, Ralf W.; Hung, Li-Wei Acta Crystallographica Section D Biological Crystallography, Vol. 58, Issue 11 https://doi.org/10.1107/S0907444902016657	journal	October 2002
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
Likelihood-enhanced fast translation functions McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Storoni, Laurent C. Acta Crystallographica Section D Biological Crystallography, Vol. 61, Issue 4 https://doi.org/10.1107/S0907444905001617	journal	March 2005
Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing Wu, X.; Zhou, T.; Zhu, J. Science, Vol. 333, Issue 6049 https://doi.org/10.1126/science.1207532	journal	August 2011
Highly Conserved Protective Epitopes on Influenza B Viruses Dreyfus, C.; Laursen, N. S.; Kwaks, T. Science, Vol. 337, Issue 6100 https://doi.org/10.1126/science.1222908	journal	August 2012
Hepatitis C Virus E2 Envelope Glycoprotein Core Structure Kong, L.; Giang, E.; Nieusma, T. Science, Vol. 342, Issue 6162 https://doi.org/10.1126/science.1243876	journal	November 2013
Chronic Hepatitis C Virus Infection Breaks Tolerance and Drives Polyclonal Expansion of Autoreactive B Cells Roughan, Jill E.; Reardon, Kathryn M.; Cogburn, Kristin E. Clinical and Vaccine Immunology, Vol. 19, Issue 7 https://doi.org/10.1128/CVI.00194-12	journal	May 2012
Novel Infectious cDNA Clones of Hepatitis C Virus Genotype 3a (Strain S52) and 4a (Strain ED43): Genetic Analyses and In Vivo Pathogenesis Studies Gottwein, J. M.; Scheel, T. K. H.; Callendret, B. Journal of Virology, Vol. 84, Issue 10 https://doi.org/10.1128/JVI.02667-09	journal	March 2010
Antiviral treatment of hepatitis C Feeney, E. R.; Chung, R. T. BMJ, Vol. 349, Issue jul07 3 https://doi.org/10.1136/bmj.g3308	journal	July 2014
HVR1-mediated antibody evasion of highly infectious in vivo adapted HCV in humanised mice Prentoe, Jannick; Verhoye, Lieven; Velázquez Moctezuma, Rodrigo Gut, Vol. 65, Issue 12 https://doi.org/10.1136/gutjnl-2015-310300	journal	November 2015
Broadly neutralizing antibodies with few somatic mutations and hepatitis C virus clearance Bailey, Justin R.; Flyak, Andrew I.; Cohen, Valerie J. JCI Insight, Vol. 2, Issue 9 https://doi.org/10.1172/jci.insight.92872	journal	May 2017
V H 1-69 gene is preferentially used by hepatitis C virus–associated B cell lymphomas and by normal B cells responding to the E2 viral antigen Chan, Chunghuang Hubert; Hadlock, Kenneth G.; Foung, Steven K. H. Blood, Vol. 97, Issue 4 https://doi.org/10.1182/blood.V97.4.1023	journal	February 2001
Human Monoclonal Antibodies to a Novel Cluster of Conformational Epitopes on HCV E2 with Resistance to Neutralization Escape in a Genotype 2a Isolate Keck, Zhen-yong; Xia, Jinming; Wang, Yong PLoS Pathogens, Vol. 8, Issue 4 https://doi.org/10.1371/journal.ppat.1002653	journal	April 2012
Glycan Shielding and Modulation of Hepatitis C Virus Neutralizing Antibodies Lavie, Muriel; Hanoulle, Xavier; Dubuisson, Jean Frontiers in Immunology, Vol. 9 https://doi.org/10.3389/fimmu.2018.00910	journal	April 2018
The Prevalence of Hepatitis C Virus Infection in the United States, 1999 through 2002 Armstrong, Gregory L.; Wasley, Annemarie; Simard, Edgar P. Annals of Internal Medicine, Vol. 144, Issue 10 https://doi.org/10.7326/0003-4819-144-10-200605160-00004	journal	May 2006

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