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

Nucleoprotein (N) of <i>Orthonairovirus hazaraense</i> (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 (<i>MyD88</i>) 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.