Ebola virus recruits the nuclear RNA export factor NXF1 for viral mRNA export from inclusion bodies

Ebola virus (EBOV) causes severe haemorrhagic fevers in humans with limited treatment options. Virus-host interactions are promising targets for the development of broadly acting antivirals, but knowledge of host factors involved in the EBOV life cycle is very limited. However, recently we identified the nuclear RNA export factor 1 (NXF1) as host cell factor supporting the EBOV life cycle. To better understand its role in this context, we analysed the interaction of NXF1 with viral components, and performed localisation studies and functional analyses using life cycle modelling systems and virus infections. These studies revealed that NXF1 is recruited into EBOV inclusion bodies by the EBOV nucleoprotein. In these structures it binds viral mRNAs, but not viral genomic RNA, and this interaction is required for efficient trafficking of NXF1 out of inclusion bodies. Functional analyses demonstrated that NXF1 is required for a step between viral mRNA transcription and translation. Further studies suggested that this function of NXF1 may be a general feature of several negative-sense RNA viruses replicating in cytoplasmic inclusion bodies. Taken together, our results indicate that NXF1 is recruited into inclusion bodies to promote the export of viral mRNAs from these sites. This mechanism represents a new function for NXF1 in the context of virus infections and may also provide a basis for new therapeutic approaches against EBOV and other emerging viruses.