Transcriptomic analysis of human norovirus NS1-2 protein highlights a multifunctional role in murine monocytes

• Published in: BMC genomics Vol. 18; no. 1; p. 39
• Main Authors: Lateef, Zabeen, Gimenez, Gregory, Baker, Estelle S., Ward, Vernon K.
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 05.01.2017; BioMed Central
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Amino Acid Sequence; Animals; Binding sites; Caliciviridae Infections - virology; Caspase; Cell Line; Cells, Cultured; Chemokines; Cloning; Cytokines; Enzymes; Gene Expression Profiling; Gene Expression Regulation, Viral; Genetic aspects; Genetic transcription; Genomes; Genomics; Humans; Immune system; Infections; Intracellular signalling; Localization; MAP kinase; Mass spectrometry; Mice; Monocytes; Monocytes - virology; Next-generation sequencing; NF-κB protein; Norovirus; Norovirus - physiology; Pandemics; Phosphorylation; Phylogeny; Protein Conformation, alpha-Helical; Proteins; Ribonucleic acid; RNA; RNA sequencing; Scientific imaging; Signal Transduction; Signaling; Stem cells; Toll-like receptors; Toll-Like Receptors - metabolism; Transcriptome; Transcriptomics; Viral Nonstructural Proteins - chemistry; Viral Nonstructural Proteins - genetics; Viral Nonstructural Proteins - metabolism; Viruses; NS1-2; Human norovirus (HuNoV); Murine norovirus (MNV); Transcriptomic analysis; RNAseq; Disordered protein
• ISSN: 1471-2164; 1471-2164
• DOI: 10.1186/s12864-016-3417-4

The GII.4 Sydney 2012 strain of human norovirus (HuNoV) is a pandemic strain that is responsible for the majority of norovirus outbreaks in healthcare settings. The function of the non-structural (NS)1-2 protein from HuNoV is unknown. In silico analysis of human norovirus NS1-2 protein showed that it shares features with the murine NS1-2 protein, including a disordered region, a transmembrane domain and H-box and NC sequence motifs. The proteins also contain caspase cleavage and phosphorylation sites, indicating that processing and phosphorylation may be a conserved feature of norovirus NS1-2 proteins. In this study, RNA transcripts of human and murine norovirus full-length and the disordered region of NS1-2 were transfected into monocytes, and next generation sequencing was used to analyse the transcriptomic profile of cells expressing virus proteins. The profiles were then compared to the transcriptomic profile of MNV-infected cells. RNAseq analysis showed that NS1-2 proteins from human and murine noroviruses affect multiple immune systems (chemokine, cytokine, and Toll-like receptor signaling) and intracellular pathways (NFκB, MAPK, PI3K-Akt signaling) in murine monocytes. Comparison to the transcriptomic profile of MNV-infected cells indicated the pathways that NS1-2 may affect during norovirus infection.