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Lancet (London, England) Jul 2018Enteric viruses, particularly rotaviruses and noroviruses, are a leading cause of gastroenteritis worldwide. Rotaviruses primarily affect young children, accounting for... (Review)
Review
Enteric viruses, particularly rotaviruses and noroviruses, are a leading cause of gastroenteritis worldwide. Rotaviruses primarily affect young children, accounting for almost 40% of hospital admissions for diarrhoea and 200 000 deaths worldwide, with the majority of deaths occurring in developing countries. Two vaccines against rotavirus were licensed in 2006 and have been implemented in 95 countries as of April, 2018. Data from eight high-income and middle-income countries showed a 49-89% decline in rotavirus-associated hospital admissions and a 17-55% decline in all-cause gastroenteritis-associated hospital admissions among children younger than 5 years, within 2 years of vaccine introduction. Noroviruses affect people of all ages, and are a leading cause of foodborne disease and outbreaks of gastroenteritis worldwide. Prevention of norovirus infection relies on frequent hand hygiene, limiting contact with people who are infected with the virus, and disinfection of contaminated environmental surfaces. Norovirus vaccine candidates are in clinical trials; whether vaccines will provide durable protection against the range of genetically and antigenically diverse norovirus strains remains unknown. Treatment of viral gastroenteritis is based primarily on replacement of fluid and electrolytes.
Topics: Adolescent; Adult; Aged; Caliciviridae Infections; Child; Child, Preschool; Cross-Sectional Studies; Developing Countries; Gastroenteritis; Humans; Infant; Middle Aged; Norovirus; Patient Admission; Rotavirus Infections; Rotavirus Vaccines; Viral Vaccines
PubMed: 30025810
DOI: 10.1016/S0140-6736(18)31128-0 -
Viruses Nov 2021Human Norovirus is currently the main viral cause of acute gastroenteritis (AGEs) in most countries worldwide. Nearly 50 years after the discovery of the "Norwalk virus"... (Review)
Review
Human Norovirus is currently the main viral cause of acute gastroenteritis (AGEs) in most countries worldwide. Nearly 50 years after the discovery of the "Norwalk virus" by Kapikian and colleagues, the scientific and medical community continue to generate new knowledge on the full biological and disease spectrum of Norovirus infection. Nevertheless, several areas remain incompletely understood due to the serious constraints to effectively replicate and propagate the virus. Here, we present a narrated historic perspective and summarize our current knowledge, including insights and reflections on current points of interest for a broad medical community, including clinical and molecular epidemiology, viral-host-microbiota interactions, antivirals, and vaccine prototypes. We also include a reflection on the present and future impacts of the COVID-19 pandemic on Norovirus infection and disease.
Topics: Antiviral Agents; COVID-19; Caliciviridae Infections; Gastroenteritis; Gastrointestinal Microbiome; Host-Pathogen Interactions; Humans; Norovirus; SARS-CoV-2; Viral Vaccines
PubMed: 34960668
DOI: 10.3390/v13122399 -
Viruses May 2021Laboratory cultivation of viruses is critical for determining requirements for viral replication, developing detection methods, identifying drug targets, and developing... (Review)
Review
Laboratory cultivation of viruses is critical for determining requirements for viral replication, developing detection methods, identifying drug targets, and developing antivirals. Several viruses have a history of recalcitrance towards robust replication in laboratory cell lines, including human noroviruses and hepatitis B and C viruses. These viruses have tropism for tissue components of the enterohepatic circulation system: the intestine and liver, respectively. The purpose of this review is to discuss how key enterohepatic signaling molecules, bile acids (BAs), and BA receptors are involved in the replication of these viruses and how manipulation of these factors was useful in the development and/or optimization of culture systems for these viruses. BAs have replication-promoting activities through several key mechanisms: (1) affecting cellular uptake, membrane lipid composition, and endocytic acidification; (2) directly interacting with viral capsids to influence binding to cells; and (3) modulating the innate immune response. Additionally, expression of the Na-taurocholate cotransporting polypeptide BA receptor in continuous liver cell lines is critical for hepatitis B virus entry and robust replication in laboratory culture. Viruses are capable of hijacking normal cellular functions, and understanding the role of BAs and BA receptors, components of the enterohepatic system, is valuable for expanding our knowledge on the mechanisms of norovirus and hepatitis B and C virus replication.
Topics: Bile; Bile Acids and Salts; Gastrointestinal Diseases; Hepatitis B virus; Humans; Liver; Norovirus; Virus Internalization; Virus Replication
PubMed: 34071855
DOI: 10.3390/v13060998 -
Viruses Oct 2021Human norovirus (HuNoV) infection is a global health and economic burden. Currently, there are no licensed HuNoV vaccines or antiviral drugs available. The protease... (Review)
Review
Human norovirus (HuNoV) infection is a global health and economic burden. Currently, there are no licensed HuNoV vaccines or antiviral drugs available. The protease encoded by the HuNoV genome plays a critical role in virus replication by cleaving the polyprotein and is an excellent target for developing small-molecule inhibitors. The current strategy for developing HuNoV protease inhibitors is by targeting the enzyme's active site and designing inhibitors that bind to the substrate-binding pockets located near the active site. However, subtle differential conformational flexibility in response to the different substrates in the polyprotein and structural differences in the active site and substrate-binding pockets across different genogroups, hamper the development of effective broad-spectrum inhibitors. A comparative analysis of the available HuNoV protease structures may provide valuable insight for identifying novel strategies for the design and development of such inhibitors. The goal of this review is to provide such analysis together with an overview of the current status of the design and development of HuNoV protease inhibitors.
Topics: Animals; Antiviral Agents; Binding Sites; Caliciviridae Infections; Catalytic Domain; Drug Development; Genotype; Humans; Models, Molecular; Norovirus; Peptide Hydrolases; Polyproteins; Protease Inhibitors; Protein Conformation; Protein Interaction Domains and Motifs; Viral Proteins; Virus Replication
PubMed: 34696498
DOI: 10.3390/v13102069 -
Cureus Aug 2018In contemporary medical practice, approaches to infectious disease management have been primarily rooted in a pathogen-centered model. However, host genetics also... (Review)
Review
In contemporary medical practice, approaches to infectious disease management have been primarily rooted in a pathogen-centered model. However, host genetics also contribute significantly to infectious disease burden. The fast expansion of bioinformatics techniques and the popularization of the genome-wide association study (GWAS) in recent decades have allowed for rapid and affordable high-throughput genomic analyses. This review focuses on the host model of infectious disease with particular emphasis placed on the genetic variations underlying observed infectious disease predisposition. First, we introduce observational twin-twin concordance studies of diseases such as poliomyelitis, tuberculosis, and hepatitis which suggest the important role of host genetics. We review the well-established links between specific genetic alterations and predisposition to malaria ( and ), Creutzfeldt-Jacob disease (CJD), human immunodeficiency virus (HIV), and Norwalk virus. Finally, we discuss the novel findings yielded by modern GWAS studies, which suggest the strong contribution of immunologic variation in the major histocompatibility complex (MHC) to host genetic infectious disease susceptibility. Future large-scale genomic studies hold promise in providing insights into immunology-pathogen links and may allow for the development of personalized genomic approaches to infectious disease prevention and treatment.
PubMed: 30405986
DOI: 10.7759/cureus.3210 -
Viruses Oct 2021Recognition of cell-surface glycans is an important step in the attachment of several viruses to susceptible host cells. The molecular basis of glycan interactions and... (Review)
Review
Recognition of cell-surface glycans is an important step in the attachment of several viruses to susceptible host cells. The molecular basis of glycan interactions and their functional consequences are well studied for human norovirus (HuNoV), an important gastrointestinal pathogen. Histo-blood group antigens (HBGAs), a family of fucosylated carbohydrate structures that are present on the cell surface, are utilized by HuNoVs to initially bind to cells. In this review, we describe the discovery of HBGAs as genetic susceptibility factors for HuNoV infection and review biochemical and structural studies investigating HuNoV binding to different HBGA glycans. Recently, human intestinal enteroids (HIEs) were developed as a laboratory cultivation system for HuNoV. We review how the use of this novel culture system has confirmed that fucosylated HBGAs are necessary and sufficient for infection by several HuNoV strains, describe mechanisms of antibody-mediated neutralization of infection that involve blocking of HuNoV binding to HBGAs, and discuss the potential for using the HIE model to answer unresolved questions on viral interactions with HBGAs and other glycans.
Topics: Animals; Blood Group Antigens; Caliciviridae Infections; Fucosyltransferases; Glycoconjugates; Host Microbial Interactions; Humans; Intestines; Models, Molecular; Norovirus; Polysaccharides; Protein Binding; Protein Conformation; Protein Domains; Virus Attachment; Galactoside 2-alpha-L-fucosyltransferase
PubMed: 34696500
DOI: 10.3390/v13102066 -
The Journal of Infectious Diseases Aug 2015Noroviruses are a leading cause of acute gastroenteritis worldwide. Mucosal and cellular immune responses remain poorly understood, with most studies of noroviruses...
BACKGROUND
Noroviruses are a leading cause of acute gastroenteritis worldwide. Mucosal and cellular immune responses remain poorly understood, with most studies of noroviruses having focused on serological responses to infection.
METHODS
We used saliva, feces, and peripheral blood mononuclear cells collected from persons who were administered Norwalk virus (NV) to characterize mucosal (salivary and fecal immunoglobulin A [IgA]) and cellular (NV-specific IgA and immunoglobulin G [IgG] antibody-secreting cells and total and NV-specific IgA and IgG memory B cells) immune responses following infection.
RESULTS
Prechallenge levels of NV-specific salivary IgA and NV-specific memory IgG cells correlated with protection from gastroenteritis, whereas prechallenge levels of NV-specific fecal IgA correlated with a reduced viral load. Antibody-secreting cell responses were biased toward IgA, while memory B-cell responses were biased toward IgG. NV-specific memory B cells but not antibody-secreting cells persisted 180 days after infection.
CONCLUSIONS
NV-specific salivary IgA and NV-specific memory IgG cells were identified as new correlates of protection against NV gastroenteritis. Understanding the relative importance of mucosal, cellular, and humoral immunity is important in developing vaccine strategies for norovirus disease prevention.
Topics: Adult; Antibodies, Viral; Caliciviridae Infections; Feces; Gastroenteritis; Humans; Immunoglobulin A; Immunoglobulin G; Leukocytes, Mononuclear; Norwalk virus; Saliva
PubMed: 25635121
DOI: 10.1093/infdis/jiv053 -
Current Opinion in Structural Biology Jun 2017Recognition and binding to host glycans present on cellular surfaces is an initial and critical step in viral entry. Diverse families of host glycans such as histo-blood... (Review)
Review
Recognition and binding to host glycans present on cellular surfaces is an initial and critical step in viral entry. Diverse families of host glycans such as histo-blood group antigens, sialoglycans and glycosaminoglycans are recognized by viruses. Glycan binding determines virus-host specificity, tissue tropism, pathogenesis and potential for interspecies transmission. Viruses including noroviruses, rotaviruses, enteroviruses, influenza, and papillomaviruses have evolved novel strategies to bind specific glycans often in a strain-specific manner. Structural studies have been instrumental in elucidating the molecular determinants of these virus-glycan interactions, aiding in developing vaccines and antivirals targeting this key interaction. Our review focuses on these key structural aspects of virus-glycan interactions, particularly highlighting the different strain-specific strategies employed by viruses to bind host glycans.
Topics: Animals; Host-Pathogen Interactions; Humans; Polysaccharides; Virus Physiological Phenomena; Viruses
PubMed: 28591681
DOI: 10.1016/j.sbi.2017.05.007 -
Nature Communications Feb 2023Globally, most cases of gastroenteritis are caused by pandemic GII.4 human norovirus (HuNoV) strains with no approved therapies or vaccines available. The cellular...
Globally, most cases of gastroenteritis are caused by pandemic GII.4 human norovirus (HuNoV) strains with no approved therapies or vaccines available. The cellular pathways that these strains exploit for cell entry and internalization are unknown. Here, using nontransformed human jejunal enteroids (HIEs) that recapitulate the physiology of the gastrointestinal tract, we show that infectious GII.4 virions and virus-like particles are endocytosed using a unique combination of endosomal acidification-dependent clathrin-independent carriers (CLIC), acid sphingomyelinase (ASM)-mediated lysosomal exocytosis, and membrane wound repair pathways. We found that besides the known interaction of the viral capsid Protruding (P) domain with host glycans, the Shell (S) domain interacts with both galectin-3 (gal-3) and apoptosis-linked gene 2-interacting protein X (ALIX), to orchestrate GII.4 cell entry. Recognition of the viral and cellular determinants regulating HuNoV entry provides insight into the infection process of a non-enveloped virus highlighting unique pathways and targets for developing effective therapeutics.
Topics: Humans; Clathrin; Norovirus; Signal Transduction; Virus Internalization; Cell Membrane
PubMed: 36854760
DOI: 10.1038/s41467-023-36398-z