Resistance analysis of an antibody that selectively inhibits dengue virus serotype-1

Gang Zou, Petra Kukkaro, Shee Mei Lok, Jowin K W Ng, Grace K. Tan, Brendon J. Hanson, Sylvie Alonso, Paul A. MacAry, Pei-Yong Shi

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The four serotypes of dengue virus (DENV) are the causative agents of the most prevalent mosquito-borne viral disease in human. No clinically approved antiviral therapy is currently available. Therapeutic antibodies represent a viable approach for potential treatment of DENV infection. We recently isolated a human monoclonal antibody (HM14c10) that selectively neutralizes DENV serotype 1 (DENV-1), but not serotypes 2, 3, and 4. Here we report the resistance profile of DENV-1 against HM14c10 in cell culture. Escape mutant viruses readily emerged by culturing wild-type DENV-1 in the presence of the HM14c10 antibody. Sequencing of resistant viruses revealed a single T51K substitution in the domain I/II hinge region of the viral envelope protein. Residue T51 is located within the HM14c10 epitope and is highly conserved among various DENV-1 isolates. Recombinant DENV-1 containing the T51K mutation could not be neutralized by HM14c10 in vitro or in vivo. Biochemical assay revealed that the T51K mutation completely abolished the antibody binding to the DENV-1 virion. Collectively, the results demonstrate that a single amino acid change in DENV envelope protein can confer resistance to a potent antibody through abolishing the antibody-virus interaction.

Original languageEnglish (US)
Pages (from-to)216-223
Number of pages8
JournalAntiviral Research
Volume95
Issue number3
DOIs
StatePublished - Sep 2012
Externally publishedYes

Fingerprint

Dengue Virus
Antibodies
Viral Envelope Proteins
Virus Diseases
Viruses
Serogroup
Mutation
Culicidae
Virion
Antiviral Agents
Epitopes
Cell Culture Techniques
Monoclonal Antibodies
Amino Acids

Keywords

  • Dengue virus
  • Escape mutant
  • Flavivirus envelope protein
  • Neutralizing antibody
  • Virus entry

ASJC Scopus subject areas

  • Virology
  • Pharmacology

Cite this

Resistance analysis of an antibody that selectively inhibits dengue virus serotype-1. / Zou, Gang; Kukkaro, Petra; Lok, Shee Mei; Ng, Jowin K W; Tan, Grace K.; Hanson, Brendon J.; Alonso, Sylvie; MacAry, Paul A.; Shi, Pei-Yong.

In: Antiviral Research, Vol. 95, No. 3, 09.2012, p. 216-223.

Research output: Contribution to journalArticle

Zou, G, Kukkaro, P, Lok, SM, Ng, JKW, Tan, GK, Hanson, BJ, Alonso, S, MacAry, PA & Shi, P-Y 2012, 'Resistance analysis of an antibody that selectively inhibits dengue virus serotype-1', Antiviral Research, vol. 95, no. 3, pp. 216-223. https://doi.org/10.1016/j.antiviral.2012.06.010
Zou, Gang ; Kukkaro, Petra ; Lok, Shee Mei ; Ng, Jowin K W ; Tan, Grace K. ; Hanson, Brendon J. ; Alonso, Sylvie ; MacAry, Paul A. ; Shi, Pei-Yong. / Resistance analysis of an antibody that selectively inhibits dengue virus serotype-1. In: Antiviral Research. 2012 ; Vol. 95, No. 3. pp. 216-223.
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