title: 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.
abstract: 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.
authors.affiliation: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia. l.goh1@uq.edu.au.
authors.forename: Lucas Y H
authors.initials: LY
authors.lastname: Goh
authors.affiliation: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia. j.peters2@uq.edu.au.
authors.forename: Jody
authors.initials: J
authors.lastname: Hobson-Peters
authors.affiliation: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia. natalie.prow@qimrberghofer.edu.au.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Prow
authors.affiliation: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia. kelly.baker1@uqconnect.edu.au.
authors.forename: Kelly
authors.initials: K
authors.lastname: Baker
authors.affiliation: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia. thisun.piyasena@uqconnect.edu.au.
authors.forename: Thisun B H
authors.initials: TB
authors.lastname: Piyasena
authors.affiliation: Public Health Virology, Queensland Health Forensic and Scientific Services, Coopers Plain, Queensland 4108, Australia. carmel_taylor@health.qld.gov.au.
authors.forename: Carmel T
authors.initials: CT
authors.lastname: Taylor
authors.affiliation: Protein Discovery Centre, QIMR Berghofer Medical Research Institute, Herston, Queensland 4029, Australia. ashok.rana@qimr.edu.au.
authors.forename: Ashok
authors.initials: A
authors.lastname: Rana
authors.affiliation: Protein Discovery Centre, QIMR Berghofer Medical Research Institute, Herston, Queensland 4029, Australia. marcus.hastie@qimrberghofer.edu.au.
authors.forename: Marcus L
authors.initials: ML
authors.lastname: Hastie
authors.affiliation: Protein Discovery Centre, QIMR Berghofer Medical Research Institute, Herston, Queensland 4029, Australia. jeffrey.gorman@qimrberghofer.edu.au.
authors.forename: Jeff J
authors.initials: JJ
authors.lastname: Gorman
authors.affiliation: Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia. roy.hall@uq.edu.au.
authors.forename: Roy A
authors.initials: RA
authors.lastname: Hall
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002646:Chikungunya virus / Q000235:genetics / Q000276:immunology*; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D011485:Protein Binding
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D036022:Capsid Proteins; D018985:Epitopes, B-Lymphocyte
keywords: C-terminus; N-terminus; capsid protein; chikungunya virus; epitope mapping; linear B cell epitope; monoclonal antibodies