Delineating the mechanism of anti-Lassa virus GPC-A neutralizing antibodies

Enriquez, Adrian S.; Buck, Tierra K.; Li, Haoyang; Norris, Michael J.; Moon-Walker, Alex; Zandonatti, Michelle A.; Harkins, Stephanie S.; Robinson, James E.; Branco, Luis M.; Garry, Robert F.; Saphire, Erica Ollmann; Hastie, Kathryn M.

doi:10.1016/j.celrep.2022.110841

Delineating the mechanism of anti-Lassa virus GPC-A neutralizing antibodies

Journal Article · Tue May 24 00:00:00 EDT 2022 · Cell Reports

DOI:https://doi.org/10.1016/j.celrep.2022.110841· OSTI ID:1877197

Enriquez, Adrian S. ^[1]; Buck, Tierra K. ^[1]; Li, Haoyang ^[1]; Norris, Michael J. ^[1]; Moon-Walker, Alex ^[2]; Zandonatti, Michelle A. ^[1]; Harkins, Stephanie S. ^[1]; Robinson, James E. ^[3]; Branco, Luis M. ^[4]; Garry, Robert F. ^[5]; Saphire, Erica Ollmann ^[1]; Hastie, Kathryn M. ^[1]

La Jolla Institute for Immunology, CA (United States)
La Jolla Institute for Immunology, CA (United States); Harvard Univ., Boston, MA (United States); Washington Univ., St. Louis, MO (United States)
Tulane University School of Medicine, New Orleans, LA (United States)
Zalgen Labs, LLC, Germantown, MD (United States)
Zalgen Labs, LLC, Germantown, MD (United States); Tulane University School of Medicine, New Orleans, LA (United States)

Lassa virus (LASV) is the etiologic agent of Lassa Fever, a hemorrhagic disease that is endemic to West Africa. During LASV infection, LASV glycoprotein (GP) engages with multiple host receptors for cell entry. Neutralizing antibodies against GP are rare and principally target quaternary epitopes displayed only on the metastable, pre-fusion conformation of GP. Currently, the structural features of the neutralizing GPC-A antibody competition group are understudied. Structures of two GPC-A antibodies presented here demonstrate that they bind the side of the pre-fusion GP trimer, bridging the GP1 and GP2 subunits. Complementary biochemical analyses indicate that antibody 25.10C, which is broadly specific, neutralizes by inhibiting binding of the endosomal receptor LAMP1 and also by blocking membrane fusion. The other GPC-A antibody, 36.1F, which is lineage-specific, prevents LAMP1 association only. These data illuminate a site of vulnerability on LASV GP and will guide efforts to elicit broadly reactive therapeutics and vaccines.

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); Viral Hemorrhagic Fever Consortium (VHFC); Viral Hemorrhagic Fever Immunotherapeutic Consortium (VIC); National Institutes of Health (NIH)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1877197

Alternate ID(s):: OSTI ID: 1900719

Journal Information:: Cell Reports, Journal Name: Cell Reports Journal Issue: 8 Vol. 39; ISSN 2211-1247

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (51)

Acute Sensorineural Deafness in Lassa Fever Cummins, David JAMA: The Journal of the American Medical Association, Vol. 264, Issue 16 https://doi.org/10.1001/jama.1990.03450160063030	journal	October 1990
MolProbity: More and better reference data for improved all-atom structure validation: PROTEIN SCIENCE.ORG Williams, Christopher J.; Headd, Jeffrey J.; Moriarty, Nigel W. Protein Science, Vol. 27, Issue 1 https://doi.org/10.1002/pro.3330	journal	November 2017
Current developments in Coot for macromolecular model building of Electron Cryo‐microscopy and Crystallographic Data Casañal, Ana; Lohkamp, Bernhard; Emsley, Paul Protein Science, Vol. 29, Issue 4 https://doi.org/10.1002/pro.3791	journal	March 2020
UCSF ChimeraX : Structure visualization for researchers, educators, and developers Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C. Protein Science, Vol. 30, Issue 1 https://doi.org/10.1002/pro.3943	journal	October 2020
Clinical Sequencing Uncovers Origins and Evolution of Lassa Virus Andersen, Kristian G.; Shapiro, B. Jesse; Matranga, Christian B. Cell, Vol. 162, Issue 4 https://doi.org/10.1016/j.cell.2015.07.020	journal	August 2015
Convergent Structures Illuminate Features for Germline Antibody Binding and Pan-Lassa Virus Neutralization Hastie, Kathryn M.; Cross, Robert W.; Harkins, Stephanie S. Cell, Vol. 178, Issue 4 https://doi.org/10.1016/j.cell.2019.07.020	journal	August 2019
Locking the Elbow: Improved Antibody Fab Fragments as Chaperones for Structure Determination Bailey, Lucas J.; Sheehy, Kimberly M.; Dominik, Pawel K. Journal of Molecular Biology, Vol. 430, Issue 3 https://doi.org/10.1016/j.jmb.2017.12.012	journal	February 2018
Automated electron microscope tomography using robust prediction of specimen movements Mastronarde, David N. Journal of Structural Biology, Vol. 152, Issue 1 https://doi.org/10.1016/j.jsb.2005.07.007	journal	October 2005
RELION: Implementation of a Bayesian approach to cryo-EM structure determination Scheres, Sjors H. W. Journal of Structural Biology, Vol. 180, Issue 3, p. 519-530 https://doi.org/10.1016/j.jsb.2012.09.006	journal	December 2012
Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits Robinson, James E.; Hastie, Kathryn M.; Cross, Robert W. Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms11544	journal	May 2016
cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination Punjani, Ali; Rubinstein, John L.; Fleet, David J. Nature Methods, Vol. 14, Issue 3 https://doi.org/10.1038/nmeth.4169	journal	February 2017
Privateer: software for the conformational validation of carbohydrate structures Agirre, Jon; Iglesias-Fernández, Javier; Rovira, Carme Nature Structural & Molecular Biology, Vol. 22, Issue 11 https://doi.org/10.1038/nsmb.3115	journal	November 2015
Antibodies from Sierra Leonean and Nigerian Lassa fever survivors cross-react with recombinant proteins representing Lassa viruses of divergent lineages Heinrich, Megan L.; Boisen, Matthew L.; Nelson, Diana K. S. Scientific Reports, Vol. 10, Issue 1 https://doi.org/10.1038/s41598-020-72539-w	journal	September 2020
Identification of Lassa virus glycoprotein signal peptide as a trans ‐acting maturation factor Eichler, Robert; Lenz, Oliver; Strecker, Thomas EMBO reports, Vol. 4, Issue 11 https://doi.org/10.1038/sj.embor.7400002	journal	October 2003
New Hosts of The Lassa Virus Olayemi, Ayodeji; Cadar, Daniel; Magassouba, N’Faly Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep25280	journal	May 2016
Lassa Fever McCormick, Joseph B.; King, Isabel J.; Webb, Patricia A. New England Journal of Medicine, Vol. 314, Issue 1 https://doi.org/10.1056/NEJM198601023140104	journal	January 1986
A general strategy for the evolution of bond-forming enzymes using yeast display Chen, I.; Dorr, B. M.; Liu, D. R. Proceedings of the National Academy of Sciences, Vol. 108, Issue 28 https://doi.org/10.1073/pnas.1101046108	journal	June 2011
Structure of the Lassa virus glycan shield provides a model for immunological resistance Watanabe, Yasunori; Raghwani, Jayna; Allen, Joel D. Proceedings of the National Academy of Sciences, Vol. 115, Issue 28 https://doi.org/10.1073/pnas.1803990115	journal	June 2018
The Structural Basis for Methylmalonic Aciduria: THE CRYSTAL STRUCTURE OF ARCHAEAL ATP:COBALAMIN ADENOSYLTRANSFERASE Saridakis, Vivian; Yakunin, Alexander; Xu, Xiaohui Journal of Biological Chemistry, Vol. 279, Issue 22 https://doi.org/10.1074/jbc.M401395200	journal	March 2004
The targeting of Lamp1 to lysosomes is dependent on the spacing of its cytoplasmic tail tyrosine sorting motif relative to the membrane. Rohrer, J.; Schweizer, A.; Russell, D. The Journal of Cell Biology, Vol. 132, Issue 4 https://doi.org/10.1083/jcb.132.4.565	journal	February 1996
Lassa Fever in Guinea: II. Distribution and Prevalence of Lassa Virus Infection in Small Mammals Demby, Austin H.; Inapogui, Alphonse; Kargbo, Kandeh Vector-Borne and Zoonotic Diseases, Vol. 1, Issue 4 https://doi.org/10.1089/15303660160025912	journal	December 2001
Reproductive Characteristics of Mastomys natalensis and Lassa Virus Prevalence in Guinea, West Africa Fichet-Calvet, Elisabeth; LeCompte, Emilie; Koivogui, Lamine Vector-Borne and Zoonotic Diseases, Vol. 8, Issue 1 https://doi.org/10.1089/vbz.2007.0118	journal	February 2008
Jalview Version 2--a multiple sequence alignment editor and analysis workbench Waterhouse, A. M.; Procter, J. B.; Martin, D. M. A. Bioinformatics, Vol. 25, Issue 9 https://doi.org/10.1093/bioinformatics/btp033	journal	January 2009
Crystal structure of the HIV neutralizing antibody 2G12 in complex with a bacterial oligosaccharide analog of mammalian oligomannose Stanfield, Robyn L.; De Castro, Cristina; Marzaioli, Alberto M. Glycobiology, Vol. 25, Issue 4 https://doi.org/10.1093/glycob/cwu123	journal	November 2014
Matriglycan: a novel polysaccharide that links dystroglycan to the basement membrane Yoshida-Moriguchi, T.; Campbell, K. P. Glycobiology, Vol. 25, Issue 7 https://doi.org/10.1093/glycob/cwv021	journal	April 2015
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
XDS Kabsch, Wolfgang Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 2 https://doi.org/10.1107/S0907444909047337	journal	January 2010
Data processing and analysis with the autoPROC toolbox Vonrhein, Clemens; Flensburg, Claus; Keller, Peter Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 4 https://doi.org/10.1107/S0907444911007773	journal	March 2011
Real-space refinement in PHENIX for cryo-EM and crystallography Afonine, Pavel V.; Poon, Billy K.; Read, Randy J. Acta Crystallographica Section D Structural Biology, Vol. 74, Issue 6 https://doi.org/10.1107/S2059798318006551	journal	May 2018
Antibody Domain Exchange Is an Immunological Solution to Carbohydrate Cluster Recognition Calarese, D. A. Science, Vol. 300, Issue 5628 https://doi.org/10.1126/science.1083182	journal	June 2003
Dystroglycan Function Requires Xylosyl- and Glucuronyltransferase Activities of LARGE Inamori, Kei-ichiro; Yoshida-Moriguchi, Takako; Hara, Yuji Science, Vol. 335, Issue 6064 https://doi.org/10.1126/science.1214115	journal	January 2012
Lassa virus entry requires a trigger-induced receptor switch Jae, L. T.; Raaben, M.; Herbert, A. S. Science, Vol. 344, Issue 6191 https://doi.org/10.1126/science.1252480	journal	June 2014
Lassa Virus Isolation from Mastomys natalensis Rodents during an Epidemic in Sierra Leone Monath, Thomas P.; Newhouse, Verne F.; Kemp, Graham E. Science, Vol. 185, Issue 4147 https://doi.org/10.1126/science.185.4147.263	journal	July 1974
Identification of α-Dystroglycan as a Receptor for Lymphocytic Choriomeningitis Virus and Lassa Fever Virus Cao, Wei; Henry, Michael D.; Borrow, Persephone Science, Vol. 282, Issue 5396 https://doi.org/10.1126/science.282.5396.2079	journal	December 1998
Structural basis for antibody-mediated neutralization of Lassa virus Hastie, Kathryn M.; Zandonatti, Michelle A.; Kleinfelter, Lara M. Science, Vol. 356, Issue 6341 https://doi.org/10.1126/science.aam7260	journal	June 2017
Lassa Virus Cell Entry via Dystroglycan Involves an Unusual Pathway of Macropinocytosis Oppliger, Joel; Torriani, Giulia; Herrador, Antonio Journal of Virology, Vol. 90, Issue 14 https://doi.org/10.1128/JVI.00257-16	journal	May 2016
Mutational Analysis of Lassa Virus Glycoprotein Highlights Regions Required for Alpha-Dystroglycan Utilization Acciani, Marissa; Alston, Jacob T.; Zhao, Guohui Journal of Virology, Vol. 91, Issue 18 https://doi.org/10.1128/JVI.00574-17	journal	July 2017
Molecular Mechanism for LAMP1 Recognition by Lassa Virus Cohen-Dvashi, Hadas; Cohen, Nadav; Israeli, Hadar Journal of Virology, Vol. 89, Issue 15 https://doi.org/10.1128/JVI.00651-15	journal	May 2015
Phylogeography of Lassa Virus in Nigeria Ehichioya, Deborah U.; Dellicour, Simon; Pahlmann, Meike Journal of Virology, Vol. 93, Issue 21 https://doi.org/10.1128/JVI.00929-19	journal	November 2019
Role of LAMP1 Binding and pH Sensing by the Spike Complex of Lassa Virus Cohen-Dvashi, Hadas; Israeli, Hadar; Shani, Orly Journal of Virology, Vol. 90, Issue 22 https://doi.org/10.1128/JVI.01624-16	journal	September 2016
Genetic Diversity among Lassa Virus Strains Bowen, Michael D.; Rollin, Pierre E.; Ksiazek, Thomas G. Journal of Virology, Vol. 74, Issue 15 https://doi.org/10.1128/JVI.74.15.6992-7004.2000	journal	August 2000
Posttranslational Modification of -Dystroglycan, the Cellular Receptor for Arenaviruses, by the Glycosyltransferase LARGE Is Critical for Virus Binding Kunz, S.; Rojek, J. M.; Kanagawa, M. Journal of Virology, Vol. 79, Issue 22 https://doi.org/10.1128/JVI.79.22.14282-14296.2005	journal	October 2005
Lamp1 Increases the Efficiency of Lassa Virus Infection by Promoting Fusion in Less Acidic Endosomal Compartments Hulseberg, Christine E.; Fénéant, Lucie; Szymańska, Katarzyna M. mBio, Vol. 9, Issue 1 https://doi.org/10.1128/mBio.01818-17	journal	January 2018
Immune-Mediated Systemic Vasculitis as the Proposed Cause of Sudden-Onset Sensorineural Hearing Loss following Lassa Virus Exposure in Cynomolgus Macaques Cashman, Kathleen A.; Wilkinson, Eric R.; Zeng, Xiankun mBio, Vol. 9, Issue 5 https://doi.org/10.1128/mBio.01896-18	journal	November 2018
Lassa Fever in Post-Conflict Sierra Leone Shaffer, Jeffrey G.; Grant, Donald S.; Schieffelin, John S. PLoS Neglected Tropical Diseases, Vol. 8, Issue 3 https://doi.org/10.1371/journal.pntd.0002748	journal	March 2014
Genetic characterization of Lassa virus strains isolated from 2012 to 2016 in southeastern Nigeria Oloniniyi, Olamide K.; Unigwe, Uche S.; Okada, Sayaka PLOS Neglected Tropical Diseases, Vol. 12, Issue 11 https://doi.org/10.1371/journal.pntd.0006971	journal	November 2018
LCMV Glycosylation Modulates Viral Fitness and Cell Tropism Bonhomme, Cyrille J.; Knopp, Kristeene A.; Bederka, Lydia H. PLoS ONE, Vol. 8, Issue 1 https://doi.org/10.1371/journal.pone.0053273	journal	January 2013
Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection Sommerstein, Rami; Flatz, Lukas; Remy, Melissa M. PLOS Pathogens, Vol. 11, Issue 11 https://doi.org/10.1371/journal.ppat.1005276	journal	November 2015
Acidic pH-Induced Conformations and LAMP1 Binding of the Lassa Virus Glycoprotein Spike Li, Sai; Sun, Zhaoyang; Pryce, Rhys PLOS Pathogens, Vol. 12, Issue 2 https://doi.org/10.1371/journal.ppat.1005418	journal	February 2016
New Lineage of Lassa Virus, Togo, 2016 Whitmer, Shannon L. M.; Strecker, Thomas; Cadar, Daniel Emerging Infectious Diseases, Vol. 24, Issue 3 https://doi.org/10.3201/eid2403.171905	journal	March 2018
Lassa virus isolates from Mali and the Ivory Coast represent an emerging fifth lineage Manning, John T.; Forrester, Naomi; Paessler, Slobodan Frontiers in Microbiology, Vol. 6 https://doi.org/10.3389/fmicb.2015.01037	journal	October 2015

Cited By (1)

Additional file 1 of Spatio-temporal spread and evolution of Lassa virus in West Africa Wang, Xia; Ye, Xianwei; Li, Ruihua figshare https://doi.org/10.6084/m9.figshare.25414860	dataset	January 2024

Similar Records

Convergent Structures Illuminate Features for Germline Antibody Binding and Pan-Lassa Virus Neutralization

Journal Article · Thu Aug 08 00:00:00 EDT 2019 · Cell · OSTI ID:1559323

Structural basis for antibody-mediated neutralization of Lassa virus

Journal Article · Thu Jun 01 00:00:00 EDT 2017 · Science · OSTI ID:1559325

The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain

Journal Article · Mon Feb 04 23:00:00 EST 2013 · Virology · OSTI ID:22150099

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Lassa fever
Lassa virus
antibody domain swap
cryo-EM
neutralizing antibodies
pre-fusion glycoprotein
structure-based vaccine design
x-ray crystallography

Delineating the mechanism of anti-Lassa virus GPC-A neutralizing antibodies

Citation Formats

References (51)

Cited By (1)

Similar Records

Related Subjects