Department of Microbiology & Immunology, McGill University, Montreal, QC H3A 2B4, Canada.
Department of Microbiology & Immunology, University of British Columbia, 2350 Health Science Mall, Room 4.520, Vancouver, BC V6T 1Z3, Canada.
Viruses. 2024 Jul 30;16(8):1220. doi: 10.3390/v16081220.
The hepatitis C virus (HCV) co-opts many cellular factors-including proteins and microRNAs-to complete its life cycle. A cellular RNA-binding protein, poly(rC)-binding protein 2 (PCBP2), was previously shown to bind to the hepatitis C virus (HCV) genome; however, its precise role in the viral life cycle remained unclear. Herein, using the HCV cell culture (HCVcc) system and assays that isolate each step of the viral life cycle, we found that PCBP2 does not have a direct role in viral entry, translation, genome stability, or HCV RNA replication. Rather, our data suggest that PCBP2 depletion only impacts viral RNAs that can undergo genome packaging. Taken together, our data suggest that endogenous PCBP2 modulates the early steps of genome packaging, and therefore only has an indirect effect on viral translation and RNA replication, likely by increasing the translating/replicating pool of viral RNAs to the detriment of virion assembly.
丙型肝炎病毒 (HCV) 会劫持许多细胞因子，包括蛋白质和 microRNAs，以完成其生命周期。一种细胞 RNA 结合蛋白，多聚 (rC) 结合蛋白 2 (PCBP2)，先前被证明可以与丙型肝炎病毒 (HCV) 基因组结合;然而，其在病毒生命周期中的精确作用仍不清楚。在此，我们使用丙型肝炎病毒细胞培养 (HCVcc) 系统和分离病毒生命周期每个步骤的检测，发现 PCBP2 不在病毒进入、翻译、基因组稳定性或 HCV RNA 复制中起直接作用。相反，我们的数据表明，PCBP2 耗竭仅影响可以进行基因组包装的病毒 RNA。总之，我们的数据表明，内源性 PCBP2 调节基因组包装的早期步骤，因此仅对病毒翻译和 RNA 复制产生间接影响，可能通过增加病毒 RNA 的翻译/复制池来损害病毒体组装。
