Dynamics of the influenza virus genome regulated by cellular host factors

Abstract

For efficient replication of the influenza virus genome and its post-replicational processes, not only viral factors but also host-derived cellular factors (host factors) are required. The influenza virus genome exists as viral ribonucleoprotein (vRNP) complexes with viral RNA-dependent RNA polymerases and nucleoprotein (NP). Using biochemical and proteomics approaches, we have identified host factors which are required for the vRNP replication and the progeny vRNP transport. We found that MCM complex, a cellular DNA replication licensing factor, is required for successful viral genome replication. In concert with the replication reaction, the nascent RNA chains are encapsidated with NP by cellular splicing factor UAP56. Further, after nuclear export of vRNP, we revealed that vRNP is transported to the plasma membrane using cholesterol-enriched recycling endosomes through cell cycle-independent activation of the centrosome by YB-1, which is a mitotic centrosomal protein. Depletion of YB-1 shows that the cholesterol-enriched endosomes are important for clustering of viral structural proteins at lipid rafts to assemble the virus particles concomitantly with the arrival of vRNP beneath the plasma membrane.