Nuclear export of influenza virus ribonucleoproteins: identification of an export intermediate at the nuclear periphery.

A critical phase of the influenza virus life cycle is the regulated translocation of genomic ribonucleoproteins (vRNPs) from the nuclear interior, across the nuclear envelope, and into the cytoplasm. Two viral proteins, M1 and NS2, have previously been implicated as mediators of vRNP export. We show here that vRNP nuclear export is prevented by leptomycin B (LMB), an inhibitor of the cellular factor CRM1. In LMB-treated cells, vRNPs were found in a peripheral nuclear location that localized with the nuclear lamina. vRNPs were not colocalized with either M1 or NS2. In situ extraction of cells late in infection also revealed a peripheral localization of nuclear vRNPs, whereas early in infection vRNPs were dispersed throughout the nuclear interior. We believe that vRNPs at the nuclear periphery represent a novel intermediate in the influenza virus nuclear export pathway.