ABSTRACT
We report a new norovirus GII.4 variant, GII.4 Hong Kong, with low-level circulation in 4 Eurasia countries since mid-2017. Amino acid substitutions in key residues on the virus capsid associated with the emergence of pandemic noroviruses suggest that GII.4 Hong Kong has the potential to become the next pandemic variant.
Subject(s)
Caliciviridae Infections , Gastroenteritis , Norovirus , Caliciviridae Infections/epidemiology , Europe/epidemiology , Gastroenteritis/epidemiology , Genotype , Hong Kong/epidemiology , Humans , Norovirus/genetics , PhylogenyABSTRACT
We compared viral load of emerging recombinant norovirus GII.P16-GII.2 with those for pandemic GII.Pe-GII.4 and epidemic GII.P17-GII.17 genotypes among inpatients in Hong Kong. Viral load of GII.P16-GII.2 was higher than those for other genotypes in different age groups. GII.P16-GII.2 is as replication competent as the pandemic genotype, explaining its high transmissibility and widespread circulation.
Subject(s)
Caliciviridae Infections/epidemiology , Communicable Diseases, Emerging/epidemiology , Gastroenteritis/epidemiology , Norovirus/genetics , Pandemics , Adolescent , Adult , Caliciviridae Infections/virology , Child , Child, Preschool , Communicable Diseases, Emerging/virology , Female , Gastroenteritis/virology , Genotype , Hong Kong/epidemiology , Humans , Infant , Male , Middle Aged , Viral Load , Young AdultABSTRACT
We report emerging subtropical bimodal seasonality and alternating predominance of norovirus GII.4 and non-GII.4 genotypes in Hong Kong. GII.4 predominated in summer and autumn months and affected young children, whereas emergent non-GII.4 genotypes predominated in winter months and affected all age groups. This highly dynamic epidemiology should inform vaccination strategies.
ABSTRACT
MicroRNAs (miRNAs) are a family of non-coding RNAs that play crucial roles in regulating various normal cellular responses. Recent studies revealed that the canonical miRNA biogenesis pathway is subject to sophisticated regulation. Hormonal control of miRNA biogenesis by androgen and estrogen has been demonstrated, but the direct effects of the glucocorticoid receptor (GR) on miRNA biogenesis are unknown. This study revealed the role of GR in miRNA maturation. We showed that two GR agonists, dexamethasone and ginsenoside-Rg1 rapidly suppressed the expression of mature miR-15b, miR-23a, and miR-214 in human endothelial cells. RNA pulldown coupled with proteomic analysis identified GTPase-activating protein (SH3 domain) binding protein 1 (G3BP1) as one of the RNA-binding proteins mediating GR-regulated miRNA maturation. Activated GR induced phosphorylation of v-AKT Murine Thymoma Viral Oncogene Homologue (AKT) kinase, which in turn phosphorylated and promoted nuclear translocation of G3BP1. The nuclear G3BP1 bound to the G3BP1 consensus sequence located on primary miR-15b~16-2 and miR-23a~27a~24-2 to inhibit their maturation. The findings from this study have advanced our understanding of the non-genomic effects of GR in the vascular system.
Subject(s)
DNA Helicases/metabolism , MicroRNAs/genetics , Poly-ADP-Ribose Binding Proteins/metabolism , RNA Helicases/metabolism , RNA Recognition Motif Proteins/metabolism , Receptors, Glucocorticoid/metabolism , Active Transport, Cell Nucleus , Base Sequence , Binding Sites , DNA Helicases/chemistry , Endothelial Cells , Gene Expression Regulation/drug effects , Human Umbilical Vein Endothelial Cells , Humans , MicroRNAs/chemistry , MicroRNAs/metabolism , Poly-ADP-Ribose Binding Proteins/chemistry , Protein Binding/drug effects , Proto-Oncogene Proteins c-akt/metabolism , RNA Helicases/chemistry , RNA Recognition Motif Proteins/chemistry , Receptors, Glucocorticoid/agonistsABSTRACT
Norovirus is the leading cause of acute gastroenteritis worldwide. The pathogenesis of norovirus and the induced immune response remain poorly understood due to the lack of a robust virus culture system. The monolayers of two secretor-positive Chinese human intestinal enteroid (HIE) lines were challenged with two norovirus pandemic GII.4 Sydney strains. Norovirus RNA replication in supernatants and cell lysates were quantified by RT-qPCR. RNA expression levels of immune-related genes were profiled using PCR arrays. The secreted protein levels of shortlisted upregulated genes were measured in supernatants using analyte-specific enzyme-linked immunosorbent assay (ELISA). Productive norovirus replications were achieved in three (75%) out of four inoculations. The two most upregulated immune-related genes were CXCL10 (93-folds) and IFI44L (580-folds). Gene expressions of CXCL10 and IFI44L were positively correlated with the level of norovirus RNA replication (CXCL10: Spearman's r = 0.779, p < 0.05; IFI44L: r = 0.881, p < 0.01). The higher level of secreted CXCL10 and IFI44L proteins confirmed their elevated gene expression. The two genes have been reported to be upregulated in norovirus volunteer challenges and natural human infections by other viruses. Our data suggested that HIE could mimic the innate immune response elicited in natural norovirus infection and, therefore, could serve as an experimental model for future virus-host interaction and antiviral studies.
Subject(s)
Caliciviridae Infections/immunology , Chemokine CXCL10/metabolism , Intestines/virology , Tumor Suppressor Proteins/metabolism , Aged , Aged, 80 and over , Cell Line , Chemokine CXCL10/genetics , Female , Host Microbial Interactions , Humans , Immunity, Innate , Interferons/genetics , Interferons/metabolism , Intestines/immunology , Male , Middle Aged , Models, Biological , Norovirus/pathogenicity , Norovirus/physiology , Organoids/immunology , Organoids/virology , Sequence Analysis, RNA , Tumor Suppressor Proteins/genetics , Virus ReplicationABSTRACT
We report the nearly complete genome of a norovirus GII.4 Hong Kong[P31] variant (GII strain Hu/HK/2019/GII.4 Hong Kong[P31]/CUHK-NS-2200) that was detected in a patient with gastroenteritis in August 2019. The genome was sequenced by metagenomic next-generation sequencing and was found to have 92.8% nucleotide similarity to the closest GII.4 norovirus sequence in GenBank.