Human norovirus (HuNoV) gastroenteritis is a self-limiting disease that places considerable economic burden in healthcare settings. Viral non-structural (NS)1-2 protein is important for persistence of murine norovirus (MNV) in vivo, but little else is known about the protein in regards to its function in the cell during virus replication. This project uses bioinformatic and transcriptomic analysis to identify potential roles of HuNoV and MNV NS1-2 proteins during norovirus infection
NS1-2 is unique to noroviruses and has a highly disordered proline-rich N-terminus, a putative C-terminal transmembrane domain, and predicted caspase cleavage sites. The protein sequence shows homology to the NlpC/P60 superfamily of circular permutated enzymes based on the presence of H-box and NC motifs that form a Cys/His-containing catalytic domain. These permuted papain-like NlpC/P60 enzymes (PPNE) function as peptidases, amidases, and acyltransferases. In addition, they are predicted to contain lipid-binding sites and play a role in the ubiquitin pathway.
Monocytes transfected with HuNoV or MNV NS1-2 were analysed for differential gene expression by whole transcriptome analysis using the Illumina HiSeq platform. Analysis of RNA-seq data revealed multiple pathways affected by NS1-2, including cytokine and chemokine induced inflammation, Toll-like receptor pathways, and intracellular signaling pathways. HuNoV and MNV returned similar results, with the data from HuNoV NS1-2 presented.