Department of Clinical Microbiology, Umeå University, 901 85 Umeå, Sweden.
Laboratory for Molecular Infection Medicine Sweden (MIMS), within the EMBL Nordic Partnership for Molecular Medicine, Umeå University, 901 85 Umeå, Sweden.
Viruses. 2021 Oct 6;13(10):2007. doi: 10.3390/v13102007.
The 2016 Zika virus (ZIKV) epidemic illustrates the impact of flaviviruses as emerging human pathogens. For unknown reasons, ZIKV replicates more efficiently in neural progenitor cells (NPCs) than in postmitotic neurons. Here, we identified host factors used by ZIKV using the NCI-60 library of cell lines and COMPARE analysis, and cross-analyzed this library with two other libraries of host factors with importance for ZIKV infection. We identified BAF45b, a subunit of the BAF (Brg1/Brm-associated factors) protein complexes that regulate differentiation of NPCs to post-mitotic neurons. ZIKV (and other flaviviruses) infected HAP1 cells deficient in expression of BAF45b and other BAF subunits less efficiently than wildtype (WT) HAP1 cells. We concluded that subunits of the BAF complex are important for infection of ZIKV and other flavivirus. Given their function in cell and tissue differentiation, such regulators may be important determinants of tropism and pathogenesis of arthropod-borne flaviviruses.
2016 年寨卡病毒(ZIKV)疫情说明了黄病毒作为新兴人类病原体的影响。由于未知原因,ZIKV 在神经祖细胞(NPC)中的复制效率高于有丝分裂后神经元。在这里,我们使用 NCI-60 细胞系文库和 COMPARE 分析鉴定了 ZIKV 使用的宿主因子,并将该文库与另外两个对 ZIKV 感染很重要的宿主因子文库进行了交叉分析。我们鉴定了 BAF45b,它是调节 NPC 向有丝分裂后神经元分化的 BAF(Brg1/Brm 相关因子)蛋白复合物的一个亚基。ZIKV(和其他黄病毒)感染 HAP1 细胞中表达 BAF45b 和其他 BAF 亚基的缺陷比野生型(WT)HAP1 细胞更有效。我们得出结论,BAF 复合物的亚基对于 ZIKV 和其他黄病毒的感染很重要。鉴于它们在细胞和组织分化中的功能,此类调节剂可能是节肢动物传播的黄病毒的嗜性和发病机制的重要决定因素。