Influenza B and C virus NEP (NS2) proteins possess nuclear export activities

Nucleocytoplasmic transport of viral ribonucleoproteins (vRNPs) is an essen tial aspect of the replication cycle for influenza A, B, and C viruses. The se viruses replicate and transcribe their genomes in the nuclei of infected cells. During the late stages of infection, vRNPs must be exported from th e nucleus to the cytoplasm prior to transport to viral assembly sites on th e cellular plasma membrane. Previously, we demonstrated that the influenza A virus nuclear export protein (NEP, formerly referred to as the NS2 protei n) mediates the export of vRNPs. In this report, we suggest that for influe nza B and C viruses the nuclear export function is also performed by the or thologous NEP proteins (formerly referred to as the NS2 protein). The influ enza virus B and C NEP proteins interact in the yeast two-hybrid assay with a subset of nucleoporins and with the Crm1 nuclear export factor and can f unctionally replace the effector domain from the human immunodeficiency vir us type 1 Rev protein. We established a plasmid transfection system for the generation of virus-like particles (VLPs) in which a functional viral RNA- like chloramphenicol acetyltransferase (CAT) gene is delivered to a new cel l. VLPs generated in the absence of the influenza B virus NEP protein were unable to transfer the viral RNA-like CAT gene to a new cell. From these da ta, we suggest that the nuclear export of the influenza B and C vRNPs are m ediated through interaction between NEP proteins and the cellular nucleocyt oplasmic export machinery.