Goh Lucas Y H, Hobson-Peters Jody, Prow Natalie A, Baker Kelly, Piyasena Thisun B H, Taylor Carmel T, Rana Ashok, Hastie Marcus L, Gorman Jeff J, Hall Roy A
Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland 4072, Australia.
Public Health Virology, Queensland Health Forensic and Scientific Services, Coopers Plain, Queensland 4108, Australia.
Viruses. 2015 Jun 8;7(6):2943-64. doi: 10.3390/v7062754.
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.
基孔肯雅病毒(CHIKV)是一种节肢动物传播媒介,可导致人类严重的关节炎疾病,在有合适蚊媒的地区被视为严重的健康威胁。CHIKV最近导致了数百万病例,涉及40多个国家。CHIKV最近的再次出现及其对人类健康的潜在威胁激发了人们对更好地了解该病毒的生物学和发病机制的兴趣,以及对改进治疗、预防和控制措施的需求。在本研究中,我们绘制了一组先前针对CHIKV衣壳蛋白(CP)产生的11种单克隆抗体(mAb)的结合位点。使用CHIKV CP的N端和C端截短的重组形式,确定了两个推定的结合区域,位于残基1-35和140-210之间。竞争性结合还表明,五个CP特异性mAb识别了后一个结构域中的一系列重叠表位。我们还鉴定了天然CP的一种较小的、N端截短的产物,它可能代表CHIKV 26S RNA的一种替代翻译产物,并且在CHIKV复制过程中具有潜在的功能意义。我们的数据还提供了证据,证明CP的C端对于CP的真实抗原结构是必需的。这项研究表明,这些抗CP mAb将是进一步研究CHIKV CP结构和功能的有价值的研究工具。