Vector Borne Disease Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Department of Microbiology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India.
Am J Trop Med Hyg. 2020 Apr;102(4):857-868. doi: 10.4269/ajtmh.19-0481.
Chikungunya fever (CHIKF) is a major public health concern and is caused by chikungunya virus (CHIKV). In 2005, the virus was reintroduced into India, resulting in massive outbreaks in several parts of the country. During 2010 and 2016 outbreaks, we recruited 588 patients from a tertiary care hospital in New Delhi, India, during the acute phase of CHIKF; collected their blood and clinical data; and determined their arthralgic status 12 weeks post-onset of fever. We evaluated IgM/IgG CHIKV-binding antibodies and their neutralizing capacity, sequenced complete genomes of 21 CHIKV strains, and correlated mutations with patient sequelae status. We also performed infections in murine models using representative strains from each outbreak to evaluate differences in pathogenesis. Our screening and analysis revealed that patients of the 2016 outbreak developed earlier IgM and neutralizing antibody responses that were negatively correlated with sequelae, compared with 2010 patients. Mutations that correlated with human disease progression were also correlated with enhanced murine virulence and pathogenesis. Overall, our study suggests that the development of early neutralizing antibodies and sequence variation in clinical isolates are predictors of human sequelae.
基孔肯雅热（CHIKF）是一个主要的公共卫生关注点，由基孔肯雅病毒（CHIKV）引起。2005 年，该病毒重新传入印度，导致该国多个地区大规模爆发。在 2010 年和 2016 年的疫情中，我们从印度新德里的一家三级护理医院招募了 588 名 CHIKF 急性期的患者；收集了他们的血液和临床数据；并在发热后 12 周确定了他们的关节痛状态。我们评估了 IgM/IgG CHIKV 结合抗体及其中和能力，对 21 株 CHIKV 株的全基因组进行了测序，并将突变与患者后遗症状况相关联。我们还使用每个疫情的代表性菌株在鼠模型中进行了感染，以评估发病机制的差异。我们的筛选和分析表明，与 2010 年的患者相比，2016 年疫情的患者更早出现 IgM 和中和抗体反应，且这些反应与后遗症呈负相关。与人类疾病进展相关的突变也与增强的鼠毒力和发病机制相关。总的来说，我们的研究表明，早期中和抗体的产生和临床分离株的序列变异是人类后遗症的预测因子。
