Department of Virology I, National Institute of Infectious Diseases, Tokyo, Japan; Department of Internal Medicine, The University of Tokyo, Graduate School of Medicine, Tokyo, Japan.
Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan.
Antiviral Res. 2023 May;213:105582. doi: 10.1016/j.antiviral.2023.105582. Epub 2023 Mar 21.
Chandipura virus (CHPV) is a negative-sense single-stranded RNA virus known to cause fatal encephalitis outbreaks in the Indian subcontinent. The virus displays tropism towards the pediatric population and holds significant public health concerns. Currently, there is no specific, effective therapy for CHPV encephalitis. In this study, we evaluated a novel C.B-17 severe combined immunodeficiency (SCID) mouse model which can be used for pre-clinical antiviral evaluation. Inoculation of CHPV developed a lethal infection in our model. Plaque assay and immunohistochemistry detected increased viral loads and antigens in various organs, including the brain, spinal cord, adrenal glands, and whole blood. We further conducted a proof-of-concept evaluation of favipiravir in the SCID mouse model. Favipiravir treatment improved survival with pre-symptomatic (days 5-14) and post-symptomatic (days 9-18) treatment. Reduced viral loads were observed in whole blood, kidney/adrenal gland, and brain tissue with favipiravir treatment. The findings in this study demonstrate the utility of SCID mouse for in vivo drug efficacy evaluation and the potential efficacy of favipiravir against CHPV infection.
钱德普拉病毒（CHPV）是一种负义单链 RNA 病毒，已知会在印度次大陆引起致命的脑炎爆发。该病毒对儿科人群具有趋化性，并引起重大的公共卫生关注。目前，针对 CHPV 脑炎尚无特定的有效治疗方法。在这项研究中，我们评估了一种新型 C.B-17 严重联合免疫缺陷（SCID）小鼠模型，可用于临床前抗病毒评估。CHPV 的接种在我们的模型中引发了致命感染。噬斑测定和免疫组织化学检测到病毒载量和各种器官（包括大脑、脊髓、肾上腺和全血）中的抗原增加。我们进一步在 SCID 小鼠模型中对法匹拉韦进行了概念验证评估。法匹拉韦治疗可提高存活率，包括在出现症状前（第 5-14 天）和出现症状后（第 9-18 天）进行治疗。法匹拉韦治疗可降低全血、肾脏/肾上腺和脑组织中的病毒载量。这项研究的结果表明，SCID 小鼠可用于体内药物疗效评估，以及法匹拉韦对抗 CHPV 感染的潜在疗效。
