Characterization of dengue complex-reactive epitopes on dengue 3 virus envelope protein domain III

Kiyohiko Matsui, Gregory D. Gromowski, Li Li, Amy J. Schuh, James Lee, Alan Barrett

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The disease dengue (DEN) is caused by four genetically and serologically related viruses termed DENV-1, -2, -3, and -4. The DENV envelope (E) protein ectodomain can be divided into three structural domains designated ED1, ED2, and ED3. The ED3 contains the DENV type-specific and DENV complex-reactive (epitopes shared by DENV 1-4) antigenic sites. In this study the epitopes recognized by four DENV complex-reactive monoclonal antibodies (MAbs) with neutralizing activity were mapped on the DENV-3 ED3 using a combination of physical and biological techniques. Amino acid residues L306, K308, G381, I387, and W389 were critical for all four MAbs, with residues V305, E309, V310, K325, D382, A384, K386, and R391 being critical for various subsets of the MAbs. A previous study by our group (Gromowski, G.D., Barrett, N.D., Barrett, A.D., 2008. Characterization of dengue complex-specific neutralizing epitopes on the envelope protein domain III of dengue 2 virus. J. Virol 82, 8828-8837) characterized the same panel of MAbs with DENV-2. The location of the DENV complex-reactive antigenic site on the DENV-2 and DENV-3 ED3s is similar; however, the critical residues for binding are not identical. Overall, this indicates that the DENV complex-reactive antigenic site on ED3 may be similar in location, but the surprising result is that DENV 2 and 3 exhibit unique sets of residues defining the energetics of interaction to the same panel of MAbs. These results imply that the amino acid sequences of DENV define a unique interaction network among these residues in spite of the fact that all flavivirus ED3s to date assume the same structural fold.

Original languageEnglish (US)
Pages (from-to)16-20
Number of pages5
JournalVirology
Volume384
Issue number1
DOIs
StatePublished - Feb 5 2009

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Viral Envelope Proteins
Dengue Virus
Dengue
Epitopes
Monoclonal Antibodies
Catalytic Domain
Flavivirus
Amino Acid Sequence
Protein Domains
Viruses
Amino Acids
Proteins

Keywords

  • Dengue virus type3
  • Envelope protein domain III
  • Monoclonal antibodies
  • Neutralization

ASJC Scopus subject areas

  • Virology

Cite this

Characterization of dengue complex-reactive epitopes on dengue 3 virus envelope protein domain III. / Matsui, Kiyohiko; Gromowski, Gregory D.; Li, Li; Schuh, Amy J.; Lee, James; Barrett, Alan.

In: Virology, Vol. 384, No. 1, 05.02.2009, p. 16-20.

Research output: Contribution to journalArticle

Matsui, Kiyohiko ; Gromowski, Gregory D. ; Li, Li ; Schuh, Amy J. ; Lee, James ; Barrett, Alan. / Characterization of dengue complex-reactive epitopes on dengue 3 virus envelope protein domain III. In: Virology. 2009 ; Vol. 384, No. 1. pp. 16-20.
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abstract = "The disease dengue (DEN) is caused by four genetically and serologically related viruses termed DENV-1, -2, -3, and -4. The DENV envelope (E) protein ectodomain can be divided into three structural domains designated ED1, ED2, and ED3. The ED3 contains the DENV type-specific and DENV complex-reactive (epitopes shared by DENV 1-4) antigenic sites. In this study the epitopes recognized by four DENV complex-reactive monoclonal antibodies (MAbs) with neutralizing activity were mapped on the DENV-3 ED3 using a combination of physical and biological techniques. Amino acid residues L306, K308, G381, I387, and W389 were critical for all four MAbs, with residues V305, E309, V310, K325, D382, A384, K386, and R391 being critical for various subsets of the MAbs. A previous study by our group (Gromowski, G.D., Barrett, N.D., Barrett, A.D., 2008. Characterization of dengue complex-specific neutralizing epitopes on the envelope protein domain III of dengue 2 virus. J. Virol 82, 8828-8837) characterized the same panel of MAbs with DENV-2. The location of the DENV complex-reactive antigenic site on the DENV-2 and DENV-3 ED3s is similar; however, the critical residues for binding are not identical. Overall, this indicates that the DENV complex-reactive antigenic site on ED3 may be similar in location, but the surprising result is that DENV 2 and 3 exhibit unique sets of residues defining the energetics of interaction to the same panel of MAbs. These results imply that the amino acid sequences of DENV define a unique interaction network among these residues in spite of the fact that all flavivirus ED3s to date assume the same structural fold.",
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