Lobaina Yadira, Perera Yasser
Therapeutic Hepatitis B Vaccine Group, Vaccine Division, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Havana, CP 10600, Cuba.
Molecular Oncology Group, Pharmaceuticals Division, Biomedical Research Direction, Center for Genetic Engineering and Biotechnology, Havana, CP 10600, Cuba.
Infect Disord Drug Targets. 2019;19(1):2-16. doi: 10.2174/1871526518666180327124412.
B23/nucleophosmin (B23/NPM1) is an abundant multifunctional protein mainly located in the nucleolus but constantly shuttling between the nucleus and cytosol. As a consequence of its constitutive expression, intracellular dynamics and binding capacities, B23/NPM1 interacts with multiple cellular factors in different cellular compartments, but also with viral proteins from both DNA and RNA viruses. B23/NPM1 influences overall viral replication of viruses like HIV, HBV, HCV, HDV and HPV by playing functional roles in different stages of viral replication including nuclear import, viral genome transcription and assembly, as well as final particle formation. Of note, some virus modify the subcellular localization, stability and/or increases B23/NPM1 expression levels on target cells, probably to foster B23/NPM1 functions in their own replicative cycle.
This review summarizes current knowledge concerning the interaction of B23/NPM1 with several viral proteins during relevant human infections. The opportunities and challenges of targeting this well-conserved host protein as a potentially new broad antiviral treatment are discussed in detail. Importantly, although initially conceived to treat cancer, a handful of B23/NPM1 inhibitors are currently available to test on viral infection models.
As B23/NPM1 partakes in key steps of viral replication and some viral infections remain as unsolved medical needs, an appealing idea may be the expedite evaluation of B23/NPM1 inhibitors in viral infections. Furthermore, worth to be addressed is if the up-regulation of B23/NPM1 protein levels that follows persistent viral infections may be instrumental to the malignant transformation induced by virus like HBV and HCV.
B23/核磷蛋白（B23/NPM1）是一种丰富的多功能蛋白质，主要位于核仁，但不断在细胞核和细胞质之间穿梭。由于其组成性表达、细胞内动力学和结合能力，B23/NPM1在不同细胞区室中与多种细胞因子相互作用，也与DNA病毒和RNA病毒的病毒蛋白相互作用。B23/NPM1通过在病毒复制的不同阶段发挥功能作用，包括核输入、病毒基因组转录和组装以及最终颗粒形成，影响HIV、HBV、HCV、HDV和HPV等病毒的整体病毒复制。值得注意的是，一些病毒会改变靶细胞上B23/NPM1的亚细胞定位、稳定性和/或增加其表达水平，可能是为了促进B23/NPM1在其自身复制周期中的功能。
本综述总结了目前关于B23/NPM1在相关人类感染期间与几种病毒蛋白相互作用的知识。详细讨论了将这种高度保守的宿主蛋白作为潜在的新型广谱抗病毒治疗靶点的机遇和挑战。重要的是，尽管最初设想用于治疗癌症，但目前有一些B23/NPM1抑制剂可用于在病毒感染模型上进行测试。
由于B23/NPM1参与病毒复制的关键步骤，且一些病毒感染仍是未解决的医学需求，一个有吸引力的想法可能是在病毒感染中加速评估B23/NPM1抑制剂。此外，值得探讨的是，持续病毒感染后B23/NPM1蛋白水平的上调是否可能有助于HBV和HCV等病毒诱导的恶性转化。
