Type- and subcomplex-specific neutralizing antibodies against domain III of dengue virus type 2 envelope protein recognize adjacent epitopes

Soila Sukupolvi-Petty, S. Kyle Austin, Whitney E. Purtha, Theodore Oliphant, Grant E. Nybakken, Jacob J. Schlesinger, John T. Roehrig, Gregory D. Gromowski, Alan Barrett, Daved H. Fremont, Michael S. Diamond

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

Neutralization of flaviviruses in vivo correlates with the development of an antibody response against the viral envelope (E) protein. Previous studies demonstrated that monoclonal antibodies (MAbs) against an epitope on the lateral ridge of domain III (DIII) of the West Nile virus (WNV) E protein strongly protect against infection in animals. Based on X-ray crystallography and sequence analysis, an analogous type-specific neutralizing epitope for individual serotypes of the related flavivirus dengue virus (DENV) was hypothesized. Using yeast surface display of DIII variants, we defined contact residues of a panel of type-specific, subcomplex-specific, and cross-reactive MAbs that recognize DIII of DENV type 2 (DENV-2) and have different neutralizing potentials. Type-specific MAbs with neutralizing activity against DENV-2 localized to a sequence-unique epitope on the lateral ridge of DIII, centered at the FG loop near residues E383 and P384, analogous in position to that observed with WNV-specific strongly neutralizing MAbs. Subcomplex-specific MAbs that bound some but not all DENV serotypes and neutralized DENV-2 infection recognized an adjacent epitope centered on the connecting A strand of DIII at residues K305, K307, and K310. In contrast, several MAbs that had poor neutralizing activity against DENV-2 and cross-reacted with all DENV serotypes and other flaviviruses recognized an epitope with residues in the AB loop of DIII, a conserved region that is predicted to have limited accessibility on the mature virion. Overall, our experiments define adjacent and structurally distinct epitopes on DIII of DENV-2 which elicit type-specific, subcomplex-specific, and cross-reactive antibodies with different neutralizing potentials.

Original languageEnglish (US)
Pages (from-to)12816-12826
Number of pages11
JournalJournal of Virology
Volume81
Issue number23
DOIs
StatePublished - Dec 2007

Fingerprint

Viral Envelope Proteins
Dengue virus
Dengue Virus
Neutralizing Antibodies
neutralizing antibodies
epitopes
Epitopes
neutralization
monoclonal antibodies
Monoclonal Antibodies
Flavivirus
proteins
Flaviviridae
West Nile virus
serotypes
antibodies
X Ray Crystallography
Virus Diseases
virion
X-ray diffraction

ASJC Scopus subject areas

  • Immunology

Cite this

Sukupolvi-Petty, S., Austin, S. K., Purtha, W. E., Oliphant, T., Nybakken, G. E., Schlesinger, J. J., ... Diamond, M. S. (2007). Type- and subcomplex-specific neutralizing antibodies against domain III of dengue virus type 2 envelope protein recognize adjacent epitopes. Journal of Virology, 81(23), 12816-12826. https://doi.org/10.1128/JVI.00432-07

Type- and subcomplex-specific neutralizing antibodies against domain III of dengue virus type 2 envelope protein recognize adjacent epitopes. / Sukupolvi-Petty, Soila; Austin, S. Kyle; Purtha, Whitney E.; Oliphant, Theodore; Nybakken, Grant E.; Schlesinger, Jacob J.; Roehrig, John T.; Gromowski, Gregory D.; Barrett, Alan; Fremont, Daved H.; Diamond, Michael S.

In: Journal of Virology, Vol. 81, No. 23, 12.2007, p. 12816-12826.

Research output: Contribution to journalArticle

Sukupolvi-Petty, S, Austin, SK, Purtha, WE, Oliphant, T, Nybakken, GE, Schlesinger, JJ, Roehrig, JT, Gromowski, GD, Barrett, A, Fremont, DH & Diamond, MS 2007, 'Type- and subcomplex-specific neutralizing antibodies against domain III of dengue virus type 2 envelope protein recognize adjacent epitopes', Journal of Virology, vol. 81, no. 23, pp. 12816-12826. https://doi.org/10.1128/JVI.00432-07
Sukupolvi-Petty, Soila ; Austin, S. Kyle ; Purtha, Whitney E. ; Oliphant, Theodore ; Nybakken, Grant E. ; Schlesinger, Jacob J. ; Roehrig, John T. ; Gromowski, Gregory D. ; Barrett, Alan ; Fremont, Daved H. ; Diamond, Michael S. / Type- and subcomplex-specific neutralizing antibodies against domain III of dengue virus type 2 envelope protein recognize adjacent epitopes. In: Journal of Virology. 2007 ; Vol. 81, No. 23. pp. 12816-12826.
@article{c371908b36b547a0a67b807265225cfd,
title = "Type- and subcomplex-specific neutralizing antibodies against domain III of dengue virus type 2 envelope protein recognize adjacent epitopes",
abstract = "Neutralization of flaviviruses in vivo correlates with the development of an antibody response against the viral envelope (E) protein. Previous studies demonstrated that monoclonal antibodies (MAbs) against an epitope on the lateral ridge of domain III (DIII) of the West Nile virus (WNV) E protein strongly protect against infection in animals. Based on X-ray crystallography and sequence analysis, an analogous type-specific neutralizing epitope for individual serotypes of the related flavivirus dengue virus (DENV) was hypothesized. Using yeast surface display of DIII variants, we defined contact residues of a panel of type-specific, subcomplex-specific, and cross-reactive MAbs that recognize DIII of DENV type 2 (DENV-2) and have different neutralizing potentials. Type-specific MAbs with neutralizing activity against DENV-2 localized to a sequence-unique epitope on the lateral ridge of DIII, centered at the FG loop near residues E383 and P384, analogous in position to that observed with WNV-specific strongly neutralizing MAbs. Subcomplex-specific MAbs that bound some but not all DENV serotypes and neutralized DENV-2 infection recognized an adjacent epitope centered on the connecting A strand of DIII at residues K305, K307, and K310. In contrast, several MAbs that had poor neutralizing activity against DENV-2 and cross-reacted with all DENV serotypes and other flaviviruses recognized an epitope with residues in the AB loop of DIII, a conserved region that is predicted to have limited accessibility on the mature virion. Overall, our experiments define adjacent and structurally distinct epitopes on DIII of DENV-2 which elicit type-specific, subcomplex-specific, and cross-reactive antibodies with different neutralizing potentials.",
author = "Soila Sukupolvi-Petty and Austin, {S. Kyle} and Purtha, {Whitney E.} and Theodore Oliphant and Nybakken, {Grant E.} and Schlesinger, {Jacob J.} and Roehrig, {John T.} and Gromowski, {Gregory D.} and Alan Barrett and Fremont, {Daved H.} and Diamond, {Michael S.}",
year = "2007",
month = "12",
doi = "10.1128/JVI.00432-07",
language = "English (US)",
volume = "81",
pages = "12816--12826",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "23",

}

TY - JOUR

T1 - Type- and subcomplex-specific neutralizing antibodies against domain III of dengue virus type 2 envelope protein recognize adjacent epitopes

AU - Sukupolvi-Petty, Soila

AU - Austin, S. Kyle

AU - Purtha, Whitney E.

AU - Oliphant, Theodore

AU - Nybakken, Grant E.

AU - Schlesinger, Jacob J.

AU - Roehrig, John T.

AU - Gromowski, Gregory D.

AU - Barrett, Alan

AU - Fremont, Daved H.

AU - Diamond, Michael S.

PY - 2007/12

Y1 - 2007/12

N2 - Neutralization of flaviviruses in vivo correlates with the development of an antibody response against the viral envelope (E) protein. Previous studies demonstrated that monoclonal antibodies (MAbs) against an epitope on the lateral ridge of domain III (DIII) of the West Nile virus (WNV) E protein strongly protect against infection in animals. Based on X-ray crystallography and sequence analysis, an analogous type-specific neutralizing epitope for individual serotypes of the related flavivirus dengue virus (DENV) was hypothesized. Using yeast surface display of DIII variants, we defined contact residues of a panel of type-specific, subcomplex-specific, and cross-reactive MAbs that recognize DIII of DENV type 2 (DENV-2) and have different neutralizing potentials. Type-specific MAbs with neutralizing activity against DENV-2 localized to a sequence-unique epitope on the lateral ridge of DIII, centered at the FG loop near residues E383 and P384, analogous in position to that observed with WNV-specific strongly neutralizing MAbs. Subcomplex-specific MAbs that bound some but not all DENV serotypes and neutralized DENV-2 infection recognized an adjacent epitope centered on the connecting A strand of DIII at residues K305, K307, and K310. In contrast, several MAbs that had poor neutralizing activity against DENV-2 and cross-reacted with all DENV serotypes and other flaviviruses recognized an epitope with residues in the AB loop of DIII, a conserved region that is predicted to have limited accessibility on the mature virion. Overall, our experiments define adjacent and structurally distinct epitopes on DIII of DENV-2 which elicit type-specific, subcomplex-specific, and cross-reactive antibodies with different neutralizing potentials.

AB - Neutralization of flaviviruses in vivo correlates with the development of an antibody response against the viral envelope (E) protein. Previous studies demonstrated that monoclonal antibodies (MAbs) against an epitope on the lateral ridge of domain III (DIII) of the West Nile virus (WNV) E protein strongly protect against infection in animals. Based on X-ray crystallography and sequence analysis, an analogous type-specific neutralizing epitope for individual serotypes of the related flavivirus dengue virus (DENV) was hypothesized. Using yeast surface display of DIII variants, we defined contact residues of a panel of type-specific, subcomplex-specific, and cross-reactive MAbs that recognize DIII of DENV type 2 (DENV-2) and have different neutralizing potentials. Type-specific MAbs with neutralizing activity against DENV-2 localized to a sequence-unique epitope on the lateral ridge of DIII, centered at the FG loop near residues E383 and P384, analogous in position to that observed with WNV-specific strongly neutralizing MAbs. Subcomplex-specific MAbs that bound some but not all DENV serotypes and neutralized DENV-2 infection recognized an adjacent epitope centered on the connecting A strand of DIII at residues K305, K307, and K310. In contrast, several MAbs that had poor neutralizing activity against DENV-2 and cross-reacted with all DENV serotypes and other flaviviruses recognized an epitope with residues in the AB loop of DIII, a conserved region that is predicted to have limited accessibility on the mature virion. Overall, our experiments define adjacent and structurally distinct epitopes on DIII of DENV-2 which elicit type-specific, subcomplex-specific, and cross-reactive antibodies with different neutralizing potentials.

UR - http://www.scopus.com/inward/record.url?scp=36348963709&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36348963709&partnerID=8YFLogxK

U2 - 10.1128/JVI.00432-07

DO - 10.1128/JVI.00432-07

M3 - Article

C2 - 17881453

AN - SCOPUS:36348963709

VL - 81

SP - 12816

EP - 12826

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 23

ER -