Department of Biotechnology, University of Calcutta, Kolkata, India.
Department of Botany, University of Calcutta, Kolkata, India.
Biochimie. 2024 Mar;218:105-117. doi: 10.1016/j.biochi.2023.07.019. Epub 2023 Jul 28.
Chandipura Virus is an emerging tropical pathogen with a high mortality rate among children. No mode of treatment or antivirals exists against CHPV infection, due to little information regarding its host interaction. Studying viral pathogen interaction with its host can not only provide valuable information regarding its propagation strategy, but also on which host proteins interact with the virus. Identifying these proteins and understanding their role in the infection process can provide more stable anti-viral targets. In this study, we focused on identifying host factors that interact with CHPV and may play a critical role in CHPV infection. We are the first to report the successful identification of Alpha-2-Macroglobulin (A2M), a secretory protein of the host that interacts with CHPV. We also established that LRP1 (Low-density lipoprotein receptor-related protein 1) and GRP78 (Glucose regulated protein 78), receptors of A2M, also interact with CHPV. Furthermore, we could also demonstrate that knocking out A2M has a severe effect on viral infection. We conclusively show the interaction of these host proteins with CHPV. Our findings also indicate that these host proteins could play a role in viral entry into the host cell.
钱德普拉病毒是一种新兴的热带病原体,儿童死亡率很高。由于对其宿主相互作用的了解甚少,因此针对 CHPV 感染没有治疗方法或抗病毒药物。研究病毒病原体与其宿主的相互作用不仅可以提供有关其传播策略的有价值信息,还可以提供与病毒相互作用的宿主蛋白。确定这些蛋白质及其在感染过程中的作用可以提供更稳定的抗病毒靶标。在这项研究中,我们专注于鉴定与 CHPV 相互作用并可能在 CHPV 感染中起关键作用的宿主因素。我们是第一个成功鉴定出与 CHPV 相互作用的宿主分泌蛋白α-2-巨球蛋白 (A2M) 的人。我们还证实,A2M 的受体 LRP1(低密度脂蛋白受体相关蛋白 1)和 GRP78(葡萄糖调节蛋白 78)也与 CHPV 相互作用。此外,我们还可以证明敲除 A2M 对病毒感染有严重影响。我们明确表明了这些宿主蛋白与 CHPV 的相互作用。我们的研究结果还表明,这些宿主蛋白可能在病毒进入宿主细胞中发挥作用。