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The Chikungunya Virus Capsid Protein Contains Linear B Cell Epitopes in the N- and C-Terminal Regions that are Dependent on an Intact C-Terminus for Antibody Recognition

1
Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia
2
Public Health Virology, Queensland Health Forensic and Scientific Services, Coopers Plain, Queensland 4108, Australia
3
Protein Discovery Centre, QIMR Berghofer Medical Research Institute, Herston, Queensland 4029, Australia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Curt Hagedorn
Viruses 2015, 7(6), 2943-2964; https://doi.org/10.3390/v7062754
Received: 3 February 2015 / Revised: 2 April 2015 / Accepted: 29 May 2015 / Published: 8 June 2015
(This article belongs to the Section Animal Viruses)
Chikungunya virus (CHIKV) is an arthropod-borne agent that causes severe arthritic disease in humans and is considered a serious health threat in areas where competent mosquito vectors are prevalent. CHIKV has recently been responsible for several millions of cases of disease, involving over 40 countries. The recent re-emergence of CHIKV and its potential threat to human health has stimulated interest in better understanding of the biology and pathogenesis of the virus, and requirement for improved treatment, prevention and control measures. In this study, we mapped the binding sites of a panel of eleven monoclonal antibodies (mAbs) previously generated towards the capsid protein (CP) of CHIKV. Using N- and C-terminally truncated recombinant forms of the CHIKV CP, two putative binding regions, between residues 1–35 and 140–210, were identified. Competitive binding also revealed that five of the CP-specific mAbs recognized a series of overlapping epitopes in the latter domain. We also identified a smaller, N-terminally truncated product of native CP that may represent an alternative translation product of the CHIKV 26S RNA and have potential functional significance during CHIKV replication. Our data also provides evidence that the C-terminus of CP is required for authentic antigenic structure of CP. This study shows that these anti-CP mAbs will be valuable research tools for further investigating the structure and function of the CHIKV CP. View Full-Text
Keywords: chikungunya virus; monoclonal antibodies; capsid protein; epitope mapping; linear B cell epitope; C-terminus; N-terminus chikungunya virus; monoclonal antibodies; capsid protein; epitope mapping; linear B cell epitope; C-terminus; N-terminus
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Goh, L.Y.H.; Hobson-Peters, J.; Prow, N.A.; Baker, K.; Piyasena, T.B.H.; Taylor, C.T.; Rana, A.; Hastie, M.L.; Gorman, J.J.; Hall, R.A. The Chikungunya Virus Capsid Protein Contains Linear B Cell Epitopes in the N- and C-Terminal Regions that are Dependent on an Intact C-Terminus for Antibody Recognition. Viruses 2015, 7, 2943-2964.

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