Molecular Virology Laboratory, Department of Veterinary Medicine, University of Maryland, College Park, MD 20742, USA.
Department of Microbiology, Howard University College of Medicine, Washington, DC 20059, USA.
Viruses. 2023 May 27;15(6):1258. doi: 10.3390/v15061258.
Zika virus (ZIKV) is a mosquito-borne flavivirus and causes an infection associated with congenital Zika syndrome and Guillain-Barre syndrome. The mechanism of ZIKV-mediated neuropathogenesis is not well understood. In this study, we discovered that ZIKV induces degradation of the Numb protein, which plays a crucial role in neurogenesis by allowing asymmetric cell division during embryonic development. Our data show that ZIKV reduced the Numb protein level in a time- and dose-dependent manner. However, ZIKV infection appears to have minimal effect on the transcript. Treatment of ZIKV-infected cells with a proteasome inhibitor restores the Numb protein level, which suggests the involvement of the ubiquitin-proteasome pathway. In addition, ZIKV infection shortens the half-life of the Numb protein. Among the ZIKV proteins, the capsid protein significantly reduces the Numb protein level. Immunoprecipitation of the Numb protein co-precipitates the capsid protein, indicating the interaction between these two proteins. These results provide insights into the ZIKV-cell interaction that might contribute to its impact on neurogenesis.
Zika 病毒（ZIKV）是一种通过蚊子传播的黄病毒，可引起与先天性 Zika 综合征和格林-巴利综合征相关的感染。ZIKV 介导的神经发病机制尚不清楚。在这项研究中，我们发现 ZIKV 诱导 Numb 蛋白降解，Numb 蛋白在胚胎发育过程中通过允许不对称细胞分裂，对神经发生起着至关重要的作用。我们的数据表明，ZIKV 以时间和剂量依赖的方式降低 Numb 蛋白水平。然而，ZIKV 感染对 转录本的影响似乎很小。用蛋白酶体抑制剂处理 ZIKV 感染的细胞可恢复 Numb 蛋白水平，这表明泛素-蛋白酶体途径的参与。此外，ZIKV 感染缩短了 Numb 蛋白的半衰期。在 ZIKV 蛋白中，衣壳蛋白显著降低 Numb 蛋白水平。Numb 蛋白的免疫沉淀共沉淀了衣壳蛋白，表明这两种蛋白之间存在相互作用。这些结果深入了解了 ZIKV 与细胞的相互作用，这可能有助于其对神经发生的影响。
