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Title: Resistance analysis of an antibody that selectively inhibits dengue virus serotype-1
Authors: Zou, G.
Kukkaro, P. 
Lok, S.-M. 
Ng, J.K.W.
Tan, G.K. 
Hanson, B.J.
Alonso, S. 
MacAry, P.A.
Shi, P.-Y.
Keywords: Dengue virus
Escape mutant
Flavivirus envelope protein
Neutralizing antibody
Virus entry
Issue Date: Sep-2012
Citation: Zou, G., Kukkaro, P., Lok, S.-M., Ng, J.K.W., Tan, G.K., Hanson, B.J., Alonso, S., MacAry, P.A., Shi, P.-Y. (2012-09). Resistance analysis of an antibody that selectively inhibits dengue virus serotype-1. Antiviral Research 95 (3) : 216-223. ScholarBank@NUS Repository.
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. © 2012 Elsevier B.V.
Source Title: Antiviral Research
ISSN: 01663542
DOI: 10.1016/j.antiviral.2012.06.010
Appears in Collections:Staff Publications

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