College of Veterinary Medicine, Jeonbuk National University, Iksan Campus, 54596, Iksan, Republic of Korea.
College of Veterinary Medicine, Jeonbuk National University, Iksan Campus, 54596, Iksan, Republic of Korea.
Microb Pathog. 2023 May;178:106079. doi: 10.1016/j.micpath.2023.106079. Epub 2023 Mar 24.
Experimental animal model is indispensable to evaluate the prophylactic and therapeutic candidates against severe fever with thrombocytopenia syndrome virus (SFTSV). To develop a suitable mouse model for SFTSV infection, we delivered human dendritic cell-specific ICAM-3-grabbing non-integrin (hDC-SIGN) by adeno-associated virus (AAV2) and validated its susceptibility for SFTSV infection. Western blot and RT-PCR assays confirmed the expression of hDC-SIGN in transduced cell lines and a significantly increased viral infectivity was observed in cells expressing hDC-SIGN. The C57BL/6 mice transduced with AAV2 exhibited a stable hDC-SIGN expression in the organs for 7 days. Upon SFTSV challenge with 1 × 10 FAID, the mice transduced with rAAV-hDC-SIGN showed a 12.5% mortality and reduced platelet and white blood cell count in accordance with higher viral titer than control group. Liver and spleen samples collected from the transduced mice had pathological signs similar to the IFNAR mice with severe SFTSV infection. Collectively, the rAAV-hDC-SIGN transduced mouse model can be used as an accessible and promising tool for studying the SFTSV pathogenesis and pre-clinical evaluation of vaccines and therapeutics against the SFTSV infection.
实验动物模型对于评估严重发热伴血小板减少综合征病毒（SFTSV）的预防和治疗候选物是不可或缺的。为了开发用于 SFTSV 感染的合适小鼠模型，我们通过腺相关病毒（AAV2）传递人树突状细胞特异性 ICAM-3 抓取非整联蛋白（hDC-SIGN），并验证其对 SFTSV 感染的易感性。Western blot 和 RT-PCR 检测证实了转导细胞系中 hDC-SIGN 的表达，并且在表达 hDC-SIGN 的细胞中观察到病毒感染性显著增加。用 AAV2 转导的 C57BL/6 小鼠在 7 天内稳定表达 hDC-SIGN。在用 1×10 FAID 的 SFTSV 攻击后，与对照组相比，rAAV-hDC-SIGN 转导的小鼠死亡率为 12.5%，血小板和白细胞计数降低，病毒滴度更高。从转导小鼠中收集的肝和脾样本具有与 IFNAR 小鼠类似的严重 SFTSV 感染的病理特征。总之，rAAV-hDC-SIGN 转导的小鼠模型可用作研究 SFTSV 发病机制和 SFTSV 感染疫苗和治疗药物的临床前评估的一种易于获得且有前途的工具。
