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Clinical Microbiology Reviews Jan 2015Norovirus, an RNA virus of the family Caliciviridae, is a human enteric pathogen that causes substantial morbidity across both health care and community settings.... (Review)
Review
Norovirus, an RNA virus of the family Caliciviridae, is a human enteric pathogen that causes substantial morbidity across both health care and community settings. Several factors enhance the transmissibility of norovirus, including the small inoculum required to produce infection (<100 viral particles), prolonged viral shedding, and its ability to survive in the environment. In this review, we describe the basic virology and immunology of noroviruses, the clinical disease resulting from infection and its diagnosis and management, as well as host and pathogen factors that complicate vaccine development. Additionally, we discuss overall epidemiology, infection control strategies, and global reporting efforts aimed at controlling this worldwide cause of acute gastroenteritis. Prompt implementation of infection control measures remains the mainstay of norovirus outbreak management.
Topics: Caliciviridae Infections; Disease Notification; Gastroenteritis; Host-Pathogen Interactions; Norovirus; Viral Vaccines
PubMed: 25567225
DOI: 10.1128/CMR.00075-14 -
Journal of Medical Virology Nov 2016Noroviruses constitute a family of ubiquitous and highly efficient human pathogens. In spite of decades of dedicated research, human noroviruses remain a major cause of... (Review)
Review
Noroviruses constitute a family of ubiquitous and highly efficient human pathogens. In spite of decades of dedicated research, human noroviruses remain a major cause of gastroenteritis and severe diarrheal disease around the world. Recent findings have begun to unravel the complex mechanisms that regulate norovirus pathogenesis and persistent infection, including the important interplay between the virus, the host immune system, and commensal bacteria. Herein, we will summarize recent research developments regarding norovirus cell tropism, the use of M cells, and commensal bacteria to facilitate norovirus infection, and virus, host, and bacterial determinants of persistent norovirus infections. J. Med. Virol. 88:1837-1843, 2016. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Antiviral Agents; Caliciviridae Infections; Cell Culture Techniques; Enterocytes; Gastroenteritis; Host-Pathogen Interactions; Humans; Intestines; Mice; Norovirus; Symbiosis; Viral Tropism; Virus Replication
PubMed: 27110852
DOI: 10.1002/jmv.24559 -
Gut Microbes 2021Human noroviruses are the most common viral cause of acute gastroenteritis worldwide. Currently, there are no approved vaccines or specific therapeutics to treat the... (Review)
Review
Human noroviruses are the most common viral cause of acute gastroenteritis worldwide. Currently, there are no approved vaccines or specific therapeutics to treat the disease. Some obstacles delaying the development of a norovirus vaccine are: (i) the extreme diversity presented by noroviruses; (ii) our incomplete understanding of immunity to noroviruses; and (iii) the lack of a robust cell culture system or animal model for human noroviruses. Recent advances in cultivation of norovirus, novel approaches applied to viral genomics and immunity, and completion of vaccine trials and birth cohort studies have provided new information toward a better understanding of norovirus immunity. Here, we will discuss the complex relationship between norovirus diversity and correlates of protection for human noroviruses, and how this information could be used to guide the development of cross-protective vaccines.
Topics: Animals; Biodiversity; Birth Cohort; Caliciviridae Infections; Genetic Predisposition to Disease; Host Microbial Interactions; Humans; Immunity; Norovirus; Vaccines
PubMed: 33783322
DOI: 10.1080/19490976.2021.1900994 -
The Journal of General Virology Oct 2019Noroviruses are genetically diverse RNA viruses associated with acute gastroenteritis in mammalian hosts. Phylogenetically, they can be segregated into different...
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 48 (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.
Topics: Caliciviridae Infections; Gastroenteritis; Genome, Viral; Genotype; Humans; Norovirus; Phylogeny
PubMed: 31483239
DOI: 10.1099/jgv.0.001318 -
Medicinal Research Reviews May 2019Human noroviruses inflict a significant health burden on society and are responsible for approximately 699 million infections and over 200 000 estimated deaths... (Review)
Review
Human noroviruses inflict a significant health burden on society and are responsible for approximately 699 million infections and over 200 000 estimated deaths worldwide each year. Yet despite significant research efforts, approved vaccines or antivirals to combat this pathogen are still lacking. Safe and effective antivirals are not available, particularly for chronically infected immunocompromised individuals, and for prophylactic applications to protect high-risk and vulnerable populations in outbreak settings. Since the discovery of human norovirus in 1972, the lack of a cell culture system has hindered biological research and antiviral studies for many years. Recent breakthroughs in culturing human norovirus have been encouraging, however, further development and optimization of these novel methodologies are required to facilitate more robust replication levels, that will enable reliable serological and replication studies, as well as advances in antiviral development. In the last few years, considerable progress has been made toward the development of norovirus antivirals, inviting an updated review. This review focuses on potential therapeutics that have been reported since 2010, which were examined across at least two model systems used for studying human norovirus or its enzymes. In addition, we have placed emphasis on antiviral compounds with a defined chemical structure. We include a comprehensive outline of direct-acting antivirals and offer a discussion of host-modulating compounds, a rapidly expanding and promising area of antiviral research.
Topics: Animals; Antiviral Agents; Disease Models, Animal; Drug Development; Genome, Viral; Humans; Norovirus; Virus Replication
PubMed: 30584800
DOI: 10.1002/med.21545 -
Expert Review of Vaccines Jun 2020Noroviruses are a leading cause of acute gastroenteritis worldwide. An estimated 21 million illnesses in the United States and upwards of 684 million illnesses worldwide... (Review)
Review
INTRODUCTION
Noroviruses are a leading cause of acute gastroenteritis worldwide. An estimated 21 million illnesses in the United States and upwards of 684 million illnesses worldwide are attributed to norovirus infection. There are no licensed vaccines to prevent norovirus, but several candidates are in development.
AREAS COVERED
We review recent advances in molecular epidemiology of noroviruses, immunology, and in-vitro cultivation of noroviruses using human intestinal enteroids. We also provide an update on the status of norovirus vaccine candidates.
EXPERT OPINION
Molecular epidemiological studies confirm the tremendous genetic diversity of noroviruses, the continuous emergence of new recombinant strains, and the predominance of GII.4 viruses worldwide. Duration of immunity, extent of cross protection between different genotypes, and differences in strain distribution for young children compared with adults remain key knowledge gaps. Recent discoveries regarding which epitopes are targeted by neutralizing antibodies using the novel in vitro culture of human noroviruses in human intestinal enteroids are enhancing our understanding of mechanisms of protection and providing guidance for vaccine development. A future norovirus vaccine has the potential to substantially reduce the burden of illnesses due to this ubiquitous virus.
Topics: Adult; Animals; Antibodies, Neutralizing; Caliciviridae Infections; Child; Epitopes; Gastroenteritis; Genotype; Humans; Norovirus; Viral Vaccines
PubMed: 32500763
DOI: 10.1080/14760584.2020.1777860 -
Nature Apr 2023Non-enveloped viruses require cell lysis to release new virions from infected cells, suggesting that these viruses require mechanisms to induce cell death. Noroviruses...
Non-enveloped viruses require cell lysis to release new virions from infected cells, suggesting that these viruses require mechanisms to induce cell death. Noroviruses are one such group of viruses, but there is no known mechanism that causes norovirus infection-triggered cell death and lysis. Here we identify a molecular mechanism of norovirus-induced cell death. We found that the norovirus-encoded NTPase NS3 contains an N-terminal four-helix bundle domain homologous to the membrane-disruption domain of the pseudokinase mixed lineage kinase domain-like (MLKL). NS3 has a mitochondrial localization signal and thus induces cell death by targeting mitochondria. Full-length NS3 and an N-terminal fragment of the protein bound the mitochondrial membrane lipid cardiolipin, permeabilized the mitochondrial membrane and induced mitochondrial dysfunction. Both the N-terminal region and the mitochondrial localization motif of NS3 were essential for cell death, viral egress from cells and viral replication in mice. These findings suggest that noroviruses have acquired a host MLKL-like pore-forming domain to facilitate viral egress by inducing mitochondrial dysfunction.
Topics: Animals; Mice; Cell Death; Mitochondria; Norovirus; Protein Kinases; Virus Replication; Viral Proteins; Nucleoside-Triphosphatase; Protein Sorting Signals; Cardiolipins; Mitochondrial Membranes
PubMed: 36991121
DOI: 10.1038/s41586-023-05851-w -
Current Opinion in Virology Aug 2018Noroviruses are rapidly evolving RNA viruses and are generally known as the main cause of viral gastroenteritis worldwide. Particle stability is of special interest as... (Review)
Review
Noroviruses are rapidly evolving RNA viruses and are generally known as the main cause of viral gastroenteritis worldwide. Particle stability is of special interest as transmission occurs via the faecal-oral route and virions are able to persist in the environment. Studies on norovirus capsid assembly and disassembly rely mainly on norovirus-like particles. Notably, stability of several human, murine and bovine variants has been investigated revealing distinct patterns of stability and also distinct assembly mechanisms and intermediates. Gathering information on these differences and common features may deepen our understanding of norovirus emergence and can potentially be used to distinguish variants. However, more systematic studies and standardized approaches are required.
Topics: Animals; Caliciviridae Infections; Capsid Proteins; Cattle; Gastroenteritis; Genetic Variation; Humans; Mice; Norovirus; Virion; Virus Assembly
PubMed: 29857940
DOI: 10.1016/j.coviro.2018.05.003 -
Viruses Mar 2019Autophagy is an essential cellular process by which a cell degrades materials within its cytoplasm. Intracellular pathogens like viruses must deal with autophagy, either... (Review)
Review
Autophagy is an essential cellular process by which a cell degrades materials within its cytoplasm. Intracellular pathogens like viruses must deal with autophagy, either positively or negatively, for their own survival and replication. For some viruses, autophagy can even play proviral roles, helping their replication or dissemination. For other viruses, including noroviruses, the exact role of autophagy is more complex. This short review seeks to summarize the known interactions between autophagy, autophagy proteins and norovirus, and to address remaining questions relevant to these interactions.
Topics: Animals; Autophagy; Cell Line; GTP Phosphohydrolases; Host Microbial Interactions; Host-Pathogen Interactions; Humans; Interferons; Mice; Norovirus; Virus Replication
PubMed: 30871000
DOI: 10.3390/v11030244 -
Viruses May 2019Norovirus is the most common cause of non-bacterial gastroenteritis and is a burden worldwide. The increasing norovirus diversity is currently categorized into at least... (Review)
Review
Norovirus is the most common cause of non-bacterial gastroenteritis and is a burden worldwide. The increasing norovirus diversity is currently categorized into at least 10 genogroups which are further classified into more than 40 genotypes. In addition to humans, norovirus can infect a broad range of hosts including livestock, pets, and wild animals, e.g., marine mammals and bats. Little is known about norovirus infections in most non-human hosts, but the close genetic relatedness between some animal and human noroviruses coupled with lack of understanding where newly appearing human norovirus genotypes and variants are emerging from has led to the hypothesis that norovirus may not be host restricted and might be able to jump the species barrier. We have systematically reviewed the literature to describe the diversity, prevalence, and geographic distribution of noroviruses found in animals, and the pathology associated with infection. We further discuss the evidence that exists for or against interspecies transmission including surveillance data and data from in vitro and in vivo experiments.
Topics: Animals; Caliciviridae Infections; Disease Reservoirs; Geography, Medical; Global Health; Host Specificity; Humans; Norovirus; Open Reading Frames; Phylogeny; Zoonoses
PubMed: 31130647
DOI: 10.3390/v11050478