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建立和比较免疫功能正常的 C57BL/6J 小鼠两个年龄组中,使用印度分离株的基孔肯雅病毒(CHIKV)的致病性和相关神经嗜性。

Establishment and Comparison of Pathogenicity and Related Neurotropism in Two Age Groups of Immune Competent Mice, C57BL/6J Using an Indian Isolate of Chikungunya Virus (CHIKV).

机构信息

Vector Borne Diseases Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, Delhi 110067, India.

Animal House Facility, International Centre for Genetic Engineering and Biotechnology, New Delhi, Delhi 110067, India.

出版信息

Viruses. 2019 Jun 25;11(6):578. doi: 10.3390/v11060578.

Abstract

Chikungunya (CHIK) is a febrile arboviral illness caused by chikungunya virus (CHIKV) and has been identified in more than 60 countries across the globe. A major public health concern, the infection occurs as an acute febrile phase and a chronic arthralgic phase. The disease manifests differently in different age groups that can range from asymptomatic infection in the younger age group to a prolonged chronic phase in the elderly population. The present study was undertaken to evaluate strain-specific pathogenesis of ECSA genotype of CHIKV strains derived from clinical isolates in adult C57BL/6J mice model. The strain that was pathogenic and developed distinct acute and post-acute phase of CHIK infection was further evaluated for dose-dependent pathogenesis. Upon arriving on the optimal dose to induce clinical symptoms in the mice, the disease progression was evaluated across the acute and the post-acute phase of infection for a period of 15 days post-infection in two age groups of mice, namely eight weeks old and 20 weeks old mice groups. Biochemical, hematological, and virology attributes were measured and correlated to morbidity and linked neurotropism and limb thickness in the two age groups. Our results show that CHIKV exhibit strain-specific pathogenesis in C57BL/6J mice. Distinct dissimilarities were observed between the two age groups in terms of pathogenesis, viral clearance and host response to CHIKV infection.

摘要

基孔肯雅热(CHIK)是一种由基孔肯雅病毒(CHIKV)引起的发热性虫媒病毒病,已在全球 60 多个国家得到确认。作为一个主要的公共卫生关注点,该感染表现为急性发热期和慢性关节痛期。该疾病在不同年龄组的表现不同,从年轻年龄组的无症状感染到老年人群的长期慢性期。本研究旨在评估源自成年 C57BL/6J 小鼠模型临床分离株的 ECSA 基因型 CHIKV 株的菌株特异性发病机制。对具有致病性并发展出明显急性和亚急性 CHIK 感染期的菌株进行了进一步评估,以确定其剂量依赖性发病机制。在确定了能在小鼠中诱导出临床症状的最佳剂量后,在感染后 15 天的急性和亚急性感染期间,在两个年龄组的小鼠中评估疾病进展,即 8 周龄和 20 周龄小鼠组。测量了生化、血液学和病毒学特征,并将其与发病率以及两个年龄组的神经嗜性和肢体厚度相关联。我们的结果表明,CHIKV 在 C57BL/6J 小鼠中表现出菌株特异性发病机制。在发病机制、病毒清除和宿主对 CHIKV 感染的反应方面,两个年龄组之间存在明显的差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/130f/6631960/e283dacce475/viruses-11-00578-g001.jpg

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