Nuclear localisation of West Nile virus NS5 protein modulates host gene expression

Highlights

• Direct comparison of a nuclear translocated vs mutant WNV NS5 proteins showed differences in the host RNA transcriptome.

• Nuclear located NS5 results in down-regulation of host genes, involved in the immune response.

• Cytoplasmic NS5 results in upregulation of genes involved in wnt signalling, lipoprotein and fatty acid biosynthesis.

• Genes induced upon expression of NS5 alone correlated with a subset observed during WNV infection.

Abstract

The involvement of the nucleus during flavivirus infection has been observed in only a small number of cases and can be limited to primarily two viral proteins; the structural protein C and the RNA polymerase NS5. Previously we observed that by blocking nuclear transport, WNV strain Kunjin (WNV_KUN) replication is severely affected and through mutation of the identified NLS in WNV_KUN NS5 protein. In this study, we interrogated the potential nuclear functions of WNV_KUN NS5 has on the host transcriptome, by means of RNA sequencing (RNAseq). In a direct comparison between wild type and mutant NS5, it can also be determined that the nuclear translocation of NS5 results in a significant down-regulation of host genes involved in the innate immune response. When compared to published RNAseq data from WNV infection, many of these genes were overlapping indicting the role of NS5 induced transcription during infection.