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1 - 7 of 7 for "Jan Vinjé"
Advances in understanding of the innate immune response to human norovirus infection using organoid models
Norovirus is the leading cause of epidemic and endemic acute gastroenteritis worldwide and the most frequent cause of foodborne illness in the United States. There is no specific treatment for norovirus infections and therapeutic interventions are based on alleviating symptoms and limiting viral transmission. The immune response to norovirus is not completely understood and mechanistic studies have been hindered by lack of a robust cell culture system. In recent years the human intestinal enteroid/human intestinal organoid system (HIE/HIO) has enabled successful human norovirus replication. Cells derived from HIE have also successfully been subjected to genetic manipulation using viral vectors as well as CRISPR/Cas9 technology thereby allowing studies to identify antiviral signaling pathways important in controlling norovirus infection. RNA sequencing using HIE cells has been used to investigate the transcriptional landscape during norovirus infection and to identify antiviral genes important in infection. Other cell culture platforms such as the microfluidics-based gut-on-chip technology in combination with the HIE/HIO system also have the potential to address fundamental questions on innate immunity to human norovirus. In this review we highlight the recent advances in understanding the innate immune response to human norovirus infections in the HIE system including the application of advanced molecular technologies that have become available in recent years such as the CRISPR/Cas9 and RNA sequencing as well as the potential application of single cell transcriptomics viral proteomics and gut-on-a-chip technology to further elucidate innate immunity to norovirus.
Corrigendum: Updated classification of norovirus genogroups and genotypes
ICTV Virus Taxonomy Profile: Caliciviridae
The family Caliciviridae includes viruses with single-stranded positive-sense RNA genomes of 7.4–8.3 kb. The most clinically important representatives are human noroviruses which are a leading cause of acute gastroenteritis in humans. Virions are non-enveloped with icosahedral symmetry. Members of seven genera infect mammals (Lagovirus Norovirus Nebovirus Recovirus Sapovirus Valovirus and Vesivirus) members of two genera infect birds (Bavovirus and Nacovirus) and members of two genera infect fish (Minovirus and Salovirus). This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Caliciviridae which is available at ictv.global/report/caliciviridae.
Updated classification of norovirus genogroups and genotypes
Noroviruses are genetically diverse RNA viruses associated with acute gastroenteritis in mammalian hosts. Phylogenetically they can be segregated into different genogroups as well as P (polymerase)-groups and further into genotypes and P-types based on amino acid diversity of the complete VP1 gene and nucleotide diversity of the RNA-dependent RNA polymerase (RdRp) region of ORF1 respectively. In recent years several new noroviruses have been reported that warrant an update of the existing classification scheme. Using previously described 2× standard deviation (sd) criteria to group sequences into separate clusters we expanded the number of genogroups to 10 (GI-GX) and the number of genotypes to 49 (9 GI 27 GII 3 GIII 2 GIV 2 GV 2 GVI and 1 genotype each for GVII GVIII GIX [formerly GII.15] and GX). Viruses for which currently only one sequence is available in public databases were classified into tentative new genogroups (GNA1 and GNA2) and genotypes (GII.NA1 GII.NA2 and GIV.NA1) with their definitive assignment awaiting additional related sequences. Based on nucleotide diversity in the RdRp region noroviruses can be divided into 60 P-types (14 GI 37 GII 2 GIII 1 GIV 2 GV 2 GVI 1 GVII and 1 GX) 2 tentative P-groups and 14 tentative P-types. Future classification and nomenclature updates will be based on complete genome sequences and will be coordinated and disseminated by the international norovirus classification-working group.
Critical role of RIG-I and MDA5 in early and late stages of Tulane virus infection
Human noroviruses are a major cause of acute gastroenteritis worldwide but the lack of a robust cell culture system or small animal model have hampered a better understanding of innate immunity against these viruses. Tulane virus (TV) is the prototype virus of a tentative new genus Recovirus in the family Caliciviridae. Its epidemiology and biological properties most closely resemble human norovirus. The host innate immune response to RNA virus infection primarily involves pathogen-sensing toll-like receptors (TLRs) TLR3 and TLR7 and retinoic acid-inducible gene I-like receptor RIG-I and melanoma differentiation associated gene 5 (MDA5). In this study by using siRNA knockdown we report that TV infection in LLC-MK2 cells results in an early [3 h post infection (h p.i.) P<0.05] RIG-I-dependent and type I interferon-mediated antiviral response whereas an MDA5-mediated antiviral effect was observed at later (12 h p.i.; P<0.05) stages of TV replication. Induction of RIG-I and MDA5 was critical for inhibition of TV replication. Furthermore pre-activation of the RIG-I/MDA5 pathway prevented TV replication (>900-fold decrease; P<0.05) suggesting that RIG-I and MDA5 ligands could be used to develop novel preventive and therapeutic measures against norovirus.
Detection of human norovirus in intestinal biopsies from immunocompromised transplant patients
Human noroviruses (HuNoVs) can often cause chronic infections in solid organ and haematopoietic stem cell transplant (HSCT) patients. Based on histopathological changes observed during HuNoV infections the intestine is the presumed site of virus replication in patients; however the cell types infected by HuNoVs remain unknown. The objective of this study was to characterize histopathological changes during HuNoV infection and to determine the cell types that may be permissive for HuNoV replication in transplant patients. We analysed biopsies from HuNoV-infected and non-infected (control) transplant patients to assess histopathological changes in conjunction with detection of HuNoV antigens to identify the infected cell types. HuNoV infection in immunocompromised patients was associated with histopathological changes such as disorganization and flattening of the intestinal epithelium. The HuNoV major capsid protein VP1 was detected in all segments of the small intestine in areas of biopsies that showed histopathological changes. Specifically VP1 was detected in enterocytes macrophages T cells and dendritic cells. HuNoV replication was investigated by detecting the non-structural proteins RdRp and VPg. We detected RdRp and VPg along with VP1 in duodenal and jejunal enterocytes. These results provide critical insights into histological changes due to HuNoV infection in immunocompromised patients and propose human enterocytes as a physiologically relevant cell type for HuNoV cultivation.
Comparison of norovirus genogroup I, II and IV seroprevalence among children in the Netherlands, 1963, 1983 and 2006
Noroviruses are a major cause of acute gastroenteritis worldwide and are a genetically diverse group of viruses. Since 2002 an increasing number of norovirus outbreaks have been reported globally but it is not clear whether this increase has been caused by a higher awareness or reflects the emergence of new genogroup II genotype 4 (GII.4) variants. The hypothesis that norovirus prevalence has increased post-2002 and is related to the emergence of GII.4 is tested in this study. Sera collected from children aged <5 years of three Dutch cross-sectional population based cohorts in 1963 1983 and 2006/2007 (n=143 n=130 and n=376 respectively) were tested for specific serum IgG by protein array using antigens to GII.4 and a range of other antigens representing norovirus GI GII and GIV genotypes. The protein array was validated by paired sera of norovirus infected patients and supernatants of B-cell cultures with single epitope specificity. Evidence for norovirus infection was found to be common among Dutch children in each cohort but the prevalence towards different genotypes changed over time. At the genogroup level GI seroprevalence decreased significantly between 1963 and 2006/2007 while a significant increase of GII and in particular specific antibodies of the genotype GII.4 was detected in the 2006/2007 cohort. There were no children with only GII.4 antibodies in the 1963 cohort. This study shows that the high GII.4 norovirus incidence in very young children is a recent phenomenon. These findings are of importance for vaccine development and trials that are currently focusing mostly on GII.4 viruses.