The Mechanism of Differential Neutralization of Dengue Serotype 3 Strains by Monoclonal Antibody 8A1

Overview

Journal Virology

Specialty Microbiology

Date 2013 Mar 5

PMID 23453578

Citations 13

Authors

Yang Zhou

S Kyle Austin

Daved H Fremont

Boyd L Yount

Jeremy P Huynh

Aravinda M de Silva

Ralph S Baric

William B Messer

Affiliations

Soon will be listed here.

Abstract

While previous studies have demonstrated that envelope (E) glycoprotein variation between dengue viruses (DENV) genotypes can influence antibody neutralization potency, the mechanisms of variable neutralization remain incompletely understood. Here we characterize epitope antibody interactions of a DENV-3 EDIII binding mouse mAb 8A1 which displays highly variable neutralizing activity against DENV-3 genotypes. Using a DENV-3 reverse genetics platform, we characterize ability of 8A1 to bind and neutralize naturally occurring DENV-3 E genotypic variant viruses. Introduction of single and multiple amino acid mutations into the parental clone background demonstrates that mutations at positions 301 and 383 on EDIII are responsible for 8A1 differential neutralization phenotypes. ELISA and surface plasmon resonance (SPR) studies indicate differences in binding are responsible for the variable neutralization. Variability at position 301 primarily determined binding difference through influencing antibody-EDIII dissociation rate. Our findings are relevant to many groups focusing on DENV EDIII as a vaccine target.

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References

Shepard D, Suaya J, Halstead S, Nathan M, Gubler D, Mahoney R . Cost-effectiveness of a pediatric dengue vaccine. Vaccine. 2004; 22(9-10):1275-80. DOI: 10.1016/j.vaccine.2003.09.019. View

Gromowski G, Barrett N, Barrett A . Characterization of dengue virus complex-specific neutralizing epitopes on envelope protein domain III of dengue 2 virus. J Virol. 2008; 82(17):8828-37. PMC: 2519678. DOI: 10.1128/JVI.00606-08. View

Sukupolvi-Petty S, Austin S, Engle M, Brien J, Dowd K, Williams K . Structure and function analysis of therapeutic monoclonal antibodies against dengue virus type 2. J Virol. 2010; 84(18):9227-39. PMC: 2937608. DOI: 10.1128/JVI.01087-10. View

Modis Y, Ogata S, Clements D, Harrison S . A ligand-binding pocket in the dengue virus envelope glycoprotein. Proc Natl Acad Sci U S A. 2003; 100(12):6986-91. PMC: 165817. DOI: 10.1073/pnas.0832193100. View

Modis Y, Ogata S, Clements D, Harrison S . Variable surface epitopes in the crystal structure of dengue virus type 3 envelope glycoprotein. J Virol. 2004; 79(2):1223-31. PMC: 538574. DOI: 10.1128/JVI.79.2.1223-1231.2005. View

Lok S, Kostyuchenko V, Nybakken G, Holdaway H, Battisti A, Sukupolvi-Petty S . Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins. Nat Struct Mol Biol. 2008; 15(3):312-7. DOI: 10.1038/nsmb.1382. View

Dowd K, Jost C, Durbin A, Whitehead S, Pierson T . A dynamic landscape for antibody binding modulates antibody-mediated neutralization of West Nile virus. PLoS Pathog. 2011; 7(6):e1002111. PMC: 3128118. DOI: 10.1371/journal.ppat.1002111. View

Araujo J, Nogueira R, Schatzmayr H, Zanotto P, Bello G . Phylogeography and evolutionary history of dengue virus type 3. Infect Genet Evol. 2008; 9(4):716-25. DOI: 10.1016/j.meegid.2008.10.005. View

Cockburn J, Navarro Sanchez M, Fretes N, Urvoas A, Staropoli I, Kikuti C . Mechanism of dengue virus broad cross-neutralization by a monoclonal antibody. Structure. 2012; 20(2):303-14. DOI: 10.1016/j.str.2012.01.001. View

10.

Gromowski G, Roehrig J, Diamond M, Lee J, Pitcher T, Barrett A . Mutations of an antibody binding energy hot spot on domain III of the dengue 2 envelope glycoprotein exploited for neutralization escape. Virology. 2010; 407(2):237-46. DOI: 10.1016/j.virol.2010.06.044. View

11.

Pierson T, Xu Q, Nelson S, Oliphant T, Nybakken G, Fremont D . The stoichiometry of antibody-mediated neutralization and enhancement of West Nile virus infection. Cell Host Microbe. 2007; 1(2):135-45. PMC: 2656919. DOI: 10.1016/j.chom.2007.03.002. View

12.

Lanciotti R, Lewis J, Gubler D, TRENT D . Molecular evolution and epidemiology of dengue-3 viruses. J Gen Virol. 1994; 75 ( Pt 1):65-75. DOI: 10.1099/0022-1317-75-1-65. View

13.

Shrestha B, Brien J, Sukupolvi-Petty S, Austin S, Edeling M, Kim T . The development of therapeutic antibodies that neutralize homologous and heterologous genotypes of dengue virus type 1. PLoS Pathog. 2010; 6(4):e1000823. PMC: 2848552. DOI: 10.1371/journal.ppat.1000823. View

14.

Messer W, Yount B, Hacker K, Donaldson E, Huynh J, de Silva A . Development and characterization of a reverse genetic system for studying dengue virus serotype 3 strain variation and neutralization. PLoS Negl Trop Dis. 2012; 6(2):e1486. PMC: 3289595. DOI: 10.1371/journal.pntd.0001486. View

15.

Lisova O, Hardy F, Petit V, Bedouelle H . Mapping to completeness and transplantation of a group-specific, discontinuous, neutralizing epitope in the envelope protein of dengue virus. J Gen Virol. 2007; 88(Pt 9):2387-2397. DOI: 10.1099/vir.0.83028-0. View

16.

Jiang T, Yu X, Hong W, Zhou W, Yu M, Deng Y . Co-circulation of two genotypes of dengue virus serotype 3 in Guangzhou, China, 2009. Virol J. 2012; 9:125. PMC: 3463466. DOI: 10.1186/1743-422X-9-125. View

17.

Kukreti H, Mittal V, Chaudhary A, Rautela R, Kumar M, Chauhan S . Continued persistence of a single genotype of dengue virus type-3 (DENV-3) in Delhi, India since its re-emergence over the last decade. J Microbiol Immunol Infect. 2010; 43(1):53-61. DOI: 10.1016/S1684-1182(10)60008-4. View

18.

Wahala W, Donaldson E, de Alwis R, Accavitti-Loper M, Baric R, de Silva A . Natural strain variation and antibody neutralization of dengue serotype 3 viruses. PLoS Pathog. 2010; 6(3):e1000821. PMC: 2841629. DOI: 10.1371/journal.ppat.1000821. View

19.

Cockburn J, Navarro Sanchez M, Goncalvez A, Zaitseva E, Stura E, Kikuti C . Structural insights into the neutralization mechanism of a higher primate antibody against dengue virus. EMBO J. 2011; 31(3):767-79. PMC: 3273384. DOI: 10.1038/emboj.2011.439. View

20.

Serafin I, Aaskov J . Identification of epitopes on the envelope (E) protein of dengue 2 and dengue 3 viruses using monoclonal antibodies. Arch Virol. 2002; 146(12):2469-79. DOI: 10.1007/s007050170017. View