RESULTS:
1 - 5 of 5 for "Preeti Chhabra"
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
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.
Molecular characterization of a rare G1P[19] rotavirus strain from India: evidence of reassortment between human and porcine rotavirus strains
This study pertains to the characterization of a human rotavirus strain (NIV929893) with a rare specificity of G1P[19]. Three structural genes (VP4 VP6 and VP7) and one non-structural gene (NSP4) of strain NIV929893 were subjected to RT-PCR for amplification of entire coding regions. All of the amplicons were sequenced to carry out phylogenetic analysis. The complete amino acid sequences of the VP7 and VP4 gene products showed clustering of the VP7 gene with G1 strains of human origin and the VP4 gene with P[19] strains of porcine origin. The two viral proteins VP6 and NSP4 described previously as genetically linked proteins were shown to be subgroup II and genotype B of human and porcine origins respectively. The findings of this study provide evidence of reassortment between VP7/VP6 genes of humans and VP4/NSP4 genes of porcine species and an independent segregation of VP6 and NSP4 genes in a group A human rotavirus strain with G1P[19] specificity.