The nuclear export protein of H5N1 influenza A viruses recruits M1 to the viral ribonucleoprotein to mediate nuclear export. [Microbiology]

June 2nd, 2014 by Brunotte, L., Flies, J., Bolte, H., Reuther, P., Vreede, F., Schwemmle, M.

In influenza A virus infected cells, replication and transcription of the viral genome occurs in the nucleus. In order to be packaged into viral particles at the plasma membrane, encapsidated viral genomes must be exported from the nucleus. Intriguingly, the nuclear export protein NEP is involved in both processes. While NEP stimulates viral RNA synthesis by binding to the viral polymerase, its function during nuclear export implicates interaction with vRNP-associated M1. The observation that both interactions are mediated by the C-terminal moiety of NEP raised the question whether these two features of NEP are functionally linked. Here, we provide evidence that the interaction between M1 and the vRNP depends on the NEP C-terminus and its polymerase activity-enhancing property for nuclear export of vRNPs. This suggests that these features of NEP are functionally linked. Furthermore, our data suggest that the N-terminal domain of NEP interferes with the stability of the vRNP/M1/NEP nuclear export complex, probably mediated by its highly flexible intramolecular interaction with the NEP C-terminus. Based on our data, we propose a new model for the assembly of the nuclear export complex of Influenza A virus RNPs.