Implication of B23/NPM1 in Viral Infections, Potential Uses of B23/NPM1 Inhibitors as Antiviral Therapy

摘要

Background: B23/nucleophosmin (B23/NPM1) is an abundant multifunctionalprotein mainly located in the nucleolus but constantly shuttling between the nucleus andcytosol. As a consequence of its constitutive expression, intracellular dynamics and bindingcapacities, B23/NPM1 interacts with multiple cellular factors in different cellularcompartments, but also with viral proteins from both DNA and RNA viruses. B23/NPM1influences overall viral replication of viruses like HIV, HBV, HCV, HDV and HPV byplaying functional roles in different stages of viral replication including nuclear import, viralgenome transcription and assembly, as well as final particle formation. Of note, somevirus modify the subcellular localization, stability and/or increases B23/NPM1 expressionlevels on target cells, probably to foster B23/NPM1 functions in their own replicative cycle.Results: This review summarizes current knowledge concerning the interaction ofB23/NPM1 with several viral proteins during relevant human infections. The opportunitiesand challenges of targeting this well-conserved host protein as a potentially new broadantiviral treatment are discussed in detail. Importantly, although initially conceived to treatcancer, a handful of B23/NPM1 inhibitors are currently available to test on viral infectionmodels.Conclusion: As B23/NPM1 partakes in key steps of viral replication and some viral infectionsremain as unsolved medical needs, an appealing idea may be the expedite evaluationof B23/NPM1 inhibitors in viral infections. Furthermore, worth to be addressed is ifthe up-regulation of B23/NPM1 protein levels that follows persistent viral infections maybe instrumental to the malignant transformation induced by virus like HBV and HCV.