A Structural View of Influenza Virus Ribonucleoprotein Complex and Its Functions.

Influenza viruses are a major global health threat because of their recurring seasonal burden and continuing pandemic potential. Central to the viral life cycle is the viral ribonucleoprotein complex (vRNP), the functional unit of the segmented genome, in which each negative-sense RNA segment is encapsidated by oligomeric nucleoprotein (NP) and bound at its termini by the polymerase complex (FluPol). Recent advances in structural biology have revealed high-resolution structures of FluPol in distinct conformations, NP-RNA helical assemblies, and intact vRNP architectures, providing a structural framework for understanding vRNP assembly, polymerase conformational switching, and RNA synthesis in the RNP context. By contrast, current models for vRNP trafficking and selective genome packaging still rely largely on virological, biochemical, and cell biological evidence, with only limited structural resolution. In this review, we synthesize current knowledge of vRNP assembly, transcription, replication, intracellular trafficking, and selective genome packaging, and discuss the major unresolved questions in each area as well as their implications for antiviral development.