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

Antiviral Res. 2012 Sep;95(3):216-23. doi: 10.1016/j.antiviral.2012.06.010. Epub 2012 Jul 4.


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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology*
  • Cell Line
  • DNA Mutational Analysis
  • Dengue Virus / classification
  • Dengue Virus / genetics
  • Dengue Virus / immunology*
  • Drug Resistance, Viral
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Mutant Proteins / genetics
  • Mutant Proteins / immunology
  • Mutation, Missense*
  • Protein Binding
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Mutant Proteins
  • Viral Envelope Proteins