Mathur Garvita, Mahilkar Shakuntala, Sunil Sujatha
Vector-Borne Diseases Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi 110067, India.
Vector-Borne Diseases Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi 110067, India.
Virus Res. 2025 Jun;356:199571. doi: 10.1016/j.virusres.2025.199571. Epub 2025 Apr 9.
India has witnessed several devastating chikungunya virus (CHIKV) epidemics since 2005. Developing a stable reverse genetic system using Indian CHIKV strains will be paramount to studying the molecular mechanism of CHIKV pathogenesis. We generated the first infectious clone (IC) of an Indian isolate of CHIKV and described the procedure in the present report. The IC was constructed directly using the isolate's RNA/cDNA and was further characterized after rescuing the virus. The IC exhibited characteristics similar to those of the natural isolate, such as cytopathic effect (CPE), plaque morphology, replication kinetics, and neutralization behavior. Using the same isolate, we also developed a stable IC with a reporter gene (mCherry) between double sub-genomic promoters. We further evaluated the feasibility of using this IC to test neutralization potential of CHIKV sera in 97 samples and observed that CHIKV patients' samples from India were able to neutralize this IC significantly better than an Asian genotype IC. With an impetus on vaccine and therapeutics development for CHIKV in recent years, the ICs generated through our study offer a powerful tool for evaluating several aspects of CHIKV pathogenicity and vaccine efficacy.
自2005年以来,印度已见证了几起毁灭性的基孔肯雅病毒(CHIKV)疫情。利用印度CHIKV毒株建立一个稳定的反向遗传系统对于研究CHIKV发病机制的分子机制至关重要。我们构建了首个印度CHIKV分离株的感染性克隆(IC),并在本报告中描述了该过程。该IC直接利用分离株的RNA/ cDNA构建,并在拯救病毒后进行了进一步表征。该IC表现出与天然分离株相似的特征,如细胞病变效应(CPE)、噬斑形态、复制动力学和中和行为。利用同一分离株,我们还构建了一个稳定的IC,在双亚基因组启动子之间带有一个报告基因(mCherry)。我们进一步评估了使用该IC检测97份样本中CHIKV血清中和潜力的可行性,并观察到来自印度的CHIKV患者样本比亚洲基因型IC能更好地中和该IC。近年来随着对CHIKV疫苗和治疗方法研发的推动,我们研究中产生的IC为评估CHIKV致病性和疫苗效力的多个方面提供了一个强大的工具。