Effects of Orthonairovirus hazaraense Nucleoprotein on Gene Expression Profiles in Infected Cells

Nucleoprotein (N) of Orthonairovirus hazaraense (HAZV) not only encapsidates viral genomic RNA but also has the potential to regulate functions of host factors. To screen for host factors affected by HAZV N protein, we investigated the effects of HAZV N protein on the gene expression profile by transcriptome analysis of a HAZV-infected SW13 cell line constitutively expressing HAZV N protein (SW13/N). The gene expression profile of HAZV-infected SW13/N was quite different from that of HAZV-infected SW13 cells. Notably, HAZV infection up-regulated many immune-response-related genes in SW13 cells, but not in SW13/N. This clearly indicates the suppression of host immune response by N protein. Among immune-response-related genes, the myeloid differentiation factor 88 (MyD88) gene was uniquely down-regulated in SW13/N, despite its up-regulation by HAZV infection. Furthermore, MyD88 was also down-regulated at the protein level in SW13/N. N protein was also found to potentially down-regulate cell adhesion, cell cycle, apoptosis and cytoskeleton-related genes. HAZV N protein is suggested to have a great impact on the gene expression profile in infected cells. This is the first report of comprehensive analysis of host gene expression that is manipulated by nairovirus protein.