Zhang Taoping, Xu Ruixian, Li Qiang, Jia Ting, Shi Wengang, Chen Lu, Faisal Mahmood, Gong Chunlin, Zhao Dongyi, Dai Li, Fan Lu, Song Yuzhu, Han Qinqin, Xia Xueshan, Zhang Jinyang
Research Center of Molecular Medicine of Yunnan Province, Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, PR China.
Yunnan Center for Disease Control and Prevention, Kunming 650022, PR China.
Int J Biol Macromol. 2025 May;305(Pt 1):141042. doi: 10.1016/j.ijbiomac.2025.141042. Epub 2025 Feb 14.
Rabies, caused by the rabies virus (RABV; scientific name Rabies lyssavirus), is invariably fatal, and currently, there is no specific drug for its treatment. Previous studies have demonstrated the relationship between CD9 and the RABV. However, it remains unclear whether CD9 and IL-16 affect the RABV life cycle. To verify the role of CD9 and IL-16 in the life cycle of the RABV and further explore drugs that can inhibit RABV replication. We examined the effects of overexpression or underexpression of CD9 and IL-16 on the RABV replication process. Subsequently, adeno-associated virus (AAV) vector-delivered single-chain antibodies against RABV glycoprotein (RABV-G) or IL-16, were utilized to specifically inhibit RABV replication and explore their therapeutic potential in a mouse model of rabies. Our study revealed that the CD9 protein significantly affected RABV replication in cells. Also, IL-16 could effectively inhibited the RABV replication in vitro and prolonged mouse survival in vivo. Single-chain antibodies against RABV and IL-16, delivered by AAV vectors carrying exocytotic peptides and membrane-penetrating peptides, inhibited RABV proliferation in vitro, and suppressed RABV replication in mice in vivo. The tetraspanin CD9 facilitates RABV infection, and like the RABV-G, it may also be a good therapeutic target for RABV infection. The CD9 ligand molecule IL-16 and single-chain antibodies against RABV carried by AAV delivery system are promising therapeutic approaches for RABV infection.
狂犬病由狂犬病病毒（RABV；学名狂犬病lyssavirus）引起，无一例外会导致死亡，目前尚无特效治疗药物。以往研究已证实CD9与狂犬病病毒之间的关系。然而，CD9和白细胞介素-16是否影响狂犬病病毒的生命周期仍不清楚。为了验证CD9和白细胞介素-16在狂犬病病毒生命周期中的作用，并进一步探索能够抑制狂犬病病毒复制的药物，我们检测了CD9和白细胞介素-16的过表达或低表达对狂犬病病毒复制过程的影响。随后，利用腺相关病毒（AAV）载体递送的抗狂犬病病毒糖蛋白（RABV-G）或白细胞介素-16的单链抗体，特异性抑制狂犬病病毒复制，并在狂犬病小鼠模型中探索其治疗潜力。我们的研究表明，CD9蛋白显著影响细胞内狂犬病病毒的复制。此外，白细胞介素-16在体外可有效抑制狂犬病病毒复制，并在体内延长小鼠存活时间。由携带胞吐肽和穿膜肽的AAV载体递送的抗狂犬病病毒和白细胞介素-16的单链抗体，在体外抑制狂犬病病毒增殖，并在体内抑制小鼠体内狂犬病病毒复制。四跨膜蛋白CD9促进狂犬病病毒感染，与狂犬病病毒糖蛋白一样，它也可能是狂犬病病毒感染的良好治疗靶点。CD9配体分子白细胞介素-16以及AAV递送系统携带的抗狂犬病病毒单链抗体是狂犬病病毒感染有前景的治疗方法。
