Evaluation of a novel severe combined immunodeficiency mouse model for antiviral drug evaluation against Chandipura virus infection
Evaluation of a novel severe combined immunodeficiency mouse model for antiviral drug evaluation against Chandipura virus infection
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DOI：
10.1016/j.antiviral.2023.105582
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发表时间：
2023-03-29
影响因子：
7.6
通讯作者：
Takayama-Ito，Mutsuyo
中科院分区：
文献类型：
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作者：
Kitaura，Satoshi;Tobiume，Minoru;Takayama-Ito，Mutsuyo
金迪普拉病毒 (CHPV) 是一种负义单链 RNA 病毒，已知会在印度次大陆引起致命性脑炎爆发。该病毒表现出对儿科人群的趋向性，并引起重大的公共卫生问题。目前，CHPV 脑炎尚无特异性、有效的治疗方法。在本研究中，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，该模型可用于临床前抗病毒评估。在我们的模型中，接种 CHPV 会产生致命的感染。噬菌斑测定和免疫组织化学检测到各个器官（包括大脑、脊髓、肾上腺和全血）中病毒载量和抗原增加。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。法匹拉韦治疗通过症状前（第 5-14 天）和症状后（第 9-18 天）治疗提高了生存率。法匹拉韦治疗后，全血、肾/肾上腺和脑组织中的病毒载量减少。本研究的结果证明了 SCID 小鼠在体内药效评估中的实用性以及法匹拉韦对抗 CHPV 感染的潜在功效。
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 forin vivodrug efficacy evaluation and the potential efficacy of favipiravir against CHPV infection.