Cryo-EM structures elucidate neutralizing mechanisms of anti-chikungunya human monoclonal antibodies with therapeutic activity

Proceedings of the National Academy of Sciences of the United States of America

Volumn 112, Issue 45, 2015, Pages 13898-13903

  Long, Feng ^a   Fong, Rachel H ^b   Austin, Stephen K ^c   Chen, Zhenguo ^a   Klose, Thomas ^a   Fokine, Andrei ^a   Liu, Yue ^a   Porta, Jason ^a   Sapparapu, Gopal ^d   Akahata, Wataru ^e   Doranz, Benjamin J ^b   Crowe, James E ^b,f,g   Diamond, Michael S ^c   Rossmann, Michael G ^a  

^a PURDUE UNIVERSITY   (United States)

^b Integral Molecular Inc   (United States)

^c WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d VANDERBILT UNIVERSITY   (United States)

^e VLP Therapeutics   (United States)

^f VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^g VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Chikungunya virus antibody complexes; Cryo electron microscopy structure; Neutralizing mechanism; Viral fusion inhibition

Indexed keywords

GLYCOPROTEIN E1; GLYCOPROTEIN E2; HUMAN MONOCLONAL ANTIBODY; IMMUNOGLOBULIN F(AB) FRAGMENT; MONOCLONAL ANTIBODY 4J21; MONOCLONAL ANTIBODY 5M16; NEUTRALIZING ANTIBODY; UNCLASSIFIED DRUG; MONOCLONAL ANTIBODY;

ANTIBODY COMBINING SITE; CHIKUNGUNYA; CHIKUNGUNYA VIRUS; COMPLEMENTARITY DETERMINING REGION; CONFERENCE PAPER; CONFORMATIONAL TRANSITION; CRYOELECTRON MICROSCOPY; CRYSTAL STRUCTURE; DIMERIZATION; EPITOPE MAPPING; HUMAN; HUMAN CELL; MOUSE; MUTAGENESIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN INTERACTION; RECEPTOR BINDING; SIGNAL TRANSDUCTION; VIRUS NEUTRALIZATION; VIRUS PARTICLE; CHEMISTRY; CHIKUNGUNYA FEVER; IMMUNOLOGY; PROCEDURES; PROTEIN CONFORMATION;

ANTIBODIES, MONOCLONAL; ANTIBODIES, NEUTRALIZING; CHIKUNGUNYA FEVER; CHIKUNGUNYA VIRUS; CRYOELECTRON MICROSCOPY; HUMANS; PROTEIN CONFORMATION;

EID: 84946907036     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1515558112     Document Type: Article

References (48)

1. Griffin DE (2007) Alphaviruses. Fields Virology, eds Knipe DM, Howley PM (Lippincott Williams & Wilkins, Philadelphia), 5th Ed, pp 1023-1067.
2. Kuhn RJ (2007) Togaviridae: The viruses and their replication. Fields Virology, eds Knipe DM, Howley PM (Lippincott Williams & Wilkins, Philadelphia), 5th Ed, pp 1001-1022.
3. Schilte C, et al. (2013) Chikungunya virus-associated long-term arthralgia: A 36-month prospective longitudinal study. PLoS Negl Trop Dis 7(3):e2137.
4. Staples JE, Breiman RF, Powers AM (2009) Chikungunya fever: An epidemiological review of a re-emerging infectious disease. Clin Infect Dis 49(6):942-948.
5. Robinson MC (1955) An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-1953. Trans R Soc Trop Med Hyg 49:28-32.
6. Thiboutot MM, et al. (2010) Chikungunya: A potentially emerging epidemic? PLoS Negl Trop Dis 4(4):e623.
7. Powers AM, Logue CH (2007) Changing patterns of chikungunya virus: Re-emergence of a zoonotic arbovirus. J Gen Virol 88(Pt 9):2363-2377.
8. Centers for Disease Control and Prevention (2015) NOWCAST: Chikungunya in the Americas. Available at www.cdc.gov/chikungunya/modeling/index.html. Accessed July 11, 2015.
9. Mukhopadhyay S, et al. (2006) Mapping the structure and function of the E1 and E2 glycoproteins in alphaviruses. Structure 14(1):63-73.
10. Kielian M (2006) Class II virus membrane fusion proteins. Virology 344(1):38-47.
11. Gibbons DL, et al. (2003) Visualization of the target-membrane-inserted fusion protein of Semliki Forest virus by combined electron microscopy and crystallography. Cell 114(5):573-583.
12. Simizu B, Yamamoto K, Hashimoto K, Ogata T (1984) Structural proteins of Chi-kungunya virus. J Virol 51(1):254-258.
13. Ivanova L, Le L, Schlesinger MJ (1995) Characterization of revertants of a Sindbis virus 6K gene mutant that affects proteolytic processing and virus assembly. Virus Res 39(2-3):165-179.
14. Lobigs M, Zhao HX, Garoff H (1990) Function of Semliki Forest virus E3 peptide in virus assembly: Replacement of E3 with an artificial signal peptide abolishes spike heter-odimerization and surface expression of E1. J Virol 64(9):4346-4355.
15. Ziemiecki A, Garofff H (1978) Subunit composition of the membrane glycoprotein complex of Semliki Forest virus. J Mol Biol 122(3):259-269.
16. Zhang R, et al. (2011) 4.4 Å cryo-EM structure of an enveloped alphavirus Venezuelan equine encephalitis virus. EMBO J 30(18):3854-3863.
17. Garcea RL, Gissmann L (2004) Virus-like particles as vaccines and vessels for the delivery of small molecules. Curr Opin Biotechnol 15(6):513-517.
18. Ludwig C, Wagner R (2007) Virus-like particles-universal molecular toolboxes. Curr Opin Biotechnol 18(6):537-545.
19. Roldão A, Mellado MC, Castilho LR, Carrondo MJ, Alves PM (2010) Virus-like particles in vaccine development. Expert Rev Vaccines 9(10):1149-1176.
20. Akahata W, et al. (2010) A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection. Nat Med 16(3):334-338.
21. Chang LJ, et al.; VRC 311 Study Team (2014) Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults: A phase 1 dose-escalation trial. Lancet 384(9959):2046-2052.
22. Sun S, et al. (2013) Structural analyses at pseudo atomic resolution of Chikungunya virus and antibodies show mechanisms of neutralization. eLife 2:e00435.
23. Lescar J, et al. (2001) The Fusion glycoprotein shell of Semliki Forest virus: An icosa-hedral assembly primed for fusogenic activation at endosomal pH. Cell 105(1): 137-148.
24. Rey FA, Heinz FX, Mandl C, Kunz C, Harrison SC (1995) The envelope glycoprotein from tick-borne encephalitis virus at 2 A resolution. Nature 375(6529):291-298.
25. Voss JE, et al. (2010) Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography. Nature 468(7324):709-712.
26. Li L, Jose J, Xiang Y, Kuhn RJ, Rossmann MG (2010) Structural changes of envelope proteins during alphavirus fusion. Nature 468(7324):705-708.
27. Smith TJ, et al. (1995) Putative receptor binding sites on alphaviruses as visualized by cryoelectron microscopy. Proc Natl Acad Sci USA 92(23):10648-10652.
28. Fong RH, et al. (2014) Exposure of epitope residues on the outer face of the chi-kungunya virus envelope trimer determines antibody neutralizing efficacy. J Virol 88(24):14364-14379.
29. Kam YW, et al. (2012) Longitudinal analysis of the human antibody response to Chikungunya virus infection: Implications for serodiagnosis and vaccine development. J Virol 86(23):13005-13015.
30. Pal P, et al. (2013) Development of a highly protective combination monoclonal antibody therapy against Chikungunya virus. PLoS Pathog 9(4):e1003312.
31. Selvarajah S, et al. (2013) A neutralizing monoclonal antibody targeting the acid-sensitive region in chikungunya virus E2 protects from disease. PLoS Negl Trop Dis 7(9):e2423.
32. Warter L, et al. (2011) Chikungunya virus envelope-specific human monoclonal antibodies with broad neutralization potency. J Immunol 186(5):3258-3264.
33. Hernandez R, Paredes A, Brown DT (2008) Sindbis virus conformational changes induced by a neutralizing anti-E1 monoclonal antibody. J Virol 82(12):5750-5760.
34. Porta J, et al. (2014) Locking and blocking the viral landscape of an alphavirus with neutralizing antibodies. J Virol 88(17):9616-9623.
35. Smith SA, et al. (2015) Isolation and characterization of broad and ultrapotent human monoclonal antibodies with therapeutic activity against Chikungunya virus. Cell Host Microbe 18(1):86-95.
36. Edeling MA, et al. (2014) Potent dengue virus neutralization by a therapeutic antibody with low monovalent affinity requires bivalent engagement. PLoS Pathog 10(4): e1004072.
37. Otwinowski Z, Minor W (1997) Processing of X-ray diffraction data collected in oscillation mode. Methods in Enzymology, ed Carter, Jr CW (Academic Press, New York), Vol 276, pp 307-326.
38. Kabsch W (2010) Xds. Acta Crystallogr D Biol Crystallogr 66(Pt 2):125-132.
39. McCoy AJ, et al. (2007) Phaser crystallographic software. J Appl Cryst 40(Pt 4):658-674.
40. Emsley P, Cowtan K (2004) Coot: Model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60(Pt 12 Pt 1):2126-2132.
41. Adams PD, et al. (2010) PHENIX: a comprehensive Python-based system for macro-molecular structure solution. Acta Crystallogr D Biol Crystallogr 66(Pt 2):213-221.
42. Tang G, et al. (2007) EMAN2: An extensible image processing suite for electron microscopy. J Struct Biol 157(1):38-46.
43. Ludtke SJ, Baldwin PR, Chiu W (1999) EMAN: Semiautomated software for high-resolution single-particle reconstructions. J Struct Biol 128(1):82-97.
44. Guo F, Jiang W (2014) Single particle cryo-electron microscopy and 3-D reconstruction of viruses. Electron Microscopy, Methods and Protocols, ed Kuo J (Humana Press, Springer, New York), 3rd Ed, pp 401-443.
45. Rossmann MG, Bernal R, Pletnev SV (2001) Combining electron microscopic with x-ray crystallographic structures. J Struct Biol 136(3):190-200.
46. Rossmann MG, Blow DM (1962) The detection of sub-units within the crystallographic asymmetric unit. Acta Crystallogr 15:24-31.
47. Krissinel E, Henrick K (2007) Inference of macromolecular assemblies from crystalline state. J Mol Biol 372(3):774-797.
48. Xiao C, Rossmann MG (2007) Interpretation of electron density with stereographic roadmap projections. J Struct Biol 158(2):182-187.