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PloS One 2013Noroviruses are the most common cause of acute gastroenteritis across all ages worldwide. These pathogens are generally understood to exhibit a wintertime seasonality,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Noroviruses are the most common cause of acute gastroenteritis across all ages worldwide. These pathogens are generally understood to exhibit a wintertime seasonality, though a systematic assessment of seasonal patterns has not been conducted in the era of modern diagnostics.
METHODS
We conducted a systematic review of the Pubmed Medline database for articles published between 1997 and 2011 to identify and extract data from articles reporting on monthly counts of norovirus. We conducted a descriptive analysis to document seasonal patterns of norovirus disease, and we also constructed multivariate linear models to identify factors associated with the strength of norovirus seasonality.
RESULTS
The searched identified 293 unique articles, yielding 38 case and 29 outbreak data series. Within these data series, 52.7% of cases and 41.2% of outbreaks occurred in winter months, and 78.9% of cases and 71.0% of outbreaks occurred in cool months. Both case and outbreak studies showed an earlier peak in season-year 2002-03, but not in season-year 2006-07, years when new genogroup II type 4 variants emerged. For outbreaks, norovirus season strength was positively associated with average rainfall in the wettest month, and inversely associated with crude birth rate in both bivariate and multivariate analyses. For cases, none of the covariates examined was associated with season strength. When case and outbreaks were combined, average rainfall in the wettest month was positively associated with season strength.
CONCLUSIONS
Norovirus is a wintertime phenomenon, at least in the temperate northern hemisphere where most data are available. Our results point to possible associations of season strength with rain in the wettest month and crude birth rate.
Topics: Animals; Internationality; Norovirus; Seasons
PubMed: 24098406
DOI: 10.1371/journal.pone.0075922 -
International Journal of Molecular... May 2023Human noroviruses (HuNoV) are major causes of acute gastroenteritis around the world. The high mutation rate and recombination potential of noroviruses are significant... (Review)
Review
Human noroviruses (HuNoV) are major causes of acute gastroenteritis around the world. The high mutation rate and recombination potential of noroviruses are significant challenges in studying the genetic diversity and evolution pattern of novel strains. In this review, we describe recent advances in the development of technologies for not only the detection but also the analysis of complete genome sequences of noroviruses and the future prospects of detection methods for tracing the evolution and genetic diversity of human noroviruses. The mechanisms of HuNoV infection and the development of antiviral drugs have been hampered by failure to develop the infectious virus in a cell model. However, recent studies have demonstrated the potential of reverse genetics for the recovery and generation of infectious viral particles, suggesting the utility of this genetics-based system as an alternative for studying the mechanisms of viral infection, such as cell entry and replication.
Topics: Humans; Norovirus; Antiviral Agents; Caliciviridae Infections
PubMed: 37240438
DOI: 10.3390/ijms24109093 -
Journal of Clinical Microbiology Feb 2015Human noroviruses are the leading cause of epidemic and sporadic gastroenteritis across all age groups. Although the disease is usually self-limiting, in the United... (Review)
Review
Human noroviruses are the leading cause of epidemic and sporadic gastroenteritis across all age groups. Although the disease is usually self-limiting, in the United States norovirus gastroenteritis causes an estimated 56,000 to 71,000 hospitalizations and 570 to 800 deaths each year. This minireview describes the latest data on laboratory methods (molecular, immunological) for norovirus detection, including real-time reverse transcription-quantitative PCR (RT-qPCR) and commercially available immunological assays as well as the latest FDA-cleared multi-gastrointestinal-pathogen platforms. In addition, an overview is provided on the latest nomenclature and molecular epidemiology of human noroviruses.
Topics: Caliciviridae Infections; Clinical Laboratory Techniques; Gastroenteritis; Genotyping Techniques; Humans; Immunoassay; Molecular Diagnostic Techniques; Molecular Epidemiology; Norovirus; Serotyping; United States
PubMed: 24989606
DOI: 10.1128/JCM.01535-14 -
Journal of Virology Apr 2023Noroviruses are the leading cause of outbreaks of acute gastroenteritis. These viruses usually interact with histo-blood group antigens (HBGAs), which are considered...
Noroviruses are the leading cause of outbreaks of acute gastroenteritis. These viruses usually interact with histo-blood group antigens (HBGAs), which are considered essential cofactors for norovirus infection. This study structurally characterizes nanobodies developed against the clinically important GII.4 and GII.17 noroviruses with a focus on the identification of novel nanobodies that efficiently block the HBGA binding site. Using X-ray crystallography, we have characterized nine different nanobodies that bound to the top, side, or bottom of the P domain. The eight nanobodies that bound to the top or side of the P domain were mainly genotype specific, while one nanobody that bound to the bottom cross-reacted against several genotypes and showed HBGA blocking potential. The four nanobodies that bound to the top of the P domain also inhibited HBGA binding, and structural analysis revealed that these nanobodies interacted with several GII.4 and GII.17 P domain residues that commonly engaged HBGAs. Moreover, these nanobody complementarity-determining regions (CDRs) extended completely into the cofactor pockets and would likely impede HBGA engagement. The atomic level information for these nanobodies and their corresponding binding sites provide a valuable template for the discovery of additional "designer" nanobodies. These next-generation nanobodies would be designed to target other important genotypes and variants, while maintaining cofactor interference. Finally, our results clearly demonstrate for the first time that nanobodies directly targeting the HBGA binding site can function as potent norovirus inhibitors. Human noroviruses are highly contagious and a major problem in closed institutions, such as schools, hospitals, and cruise ships. Reducing norovirus infections is challenging on multiple levels and includes the frequent emergence of antigenic variants, which complicates designing effective, broadly reactive capsid therapeutics. We successfully developed and characterized four norovirus nanobodies that bound at the HBGA pockets. Compared with previously developed norovirus nanobodies that inhibited HBGA through disrupted particle stability, these four novel nanobodies directly inhibited HBGA engagement and interacted with HBGA binding residues. Importantly, these new nanobodies specifically target two genotypes that have caused the majority of outbreaks worldwide and consequently would have an enormous benefit if they could be further developed as norovirus therapeutics. To date, we have structurally characterized 16 different GII nanobody complexes, a number of which block HBGA binding. These structural data could be used to design multivalent nanobody constructs with improved inhibition properties.
Topics: Blood Group Antigens; Norovirus; Single-Domain Antibodies; Binding Sites; Cross Reactions; Thermodynamics; Crystallography, X-Ray; Protein Domains; Protein Binding; Models, Molecular
PubMed: 36971561
DOI: 10.1128/jvi.01833-22 -
Clinical Infectious Diseases : An... May 2020Noroviruses are the major cause of viral gastroenteritis. Disease transmission is difficult to prevent and outbreaks in health-care facilities commonly occur. Contact...
BACKGROUND
Noroviruses are the major cause of viral gastroenteritis. Disease transmission is difficult to prevent and outbreaks in health-care facilities commonly occur. Contact with infected persons and contaminated environments are believed to be the main routes of transmission. However, noroviruses have recently been found in aerosols and airborne transmission has been suggested. The aim of our study was to investigate associations between symptoms of gastroenteritis and the presence of airborne norovirus, and to investigate the size of norovirus-carrying particles.
METHODS
Air sampling was repeatedly performed close to 26 patients with norovirus infections. Samples were analyzed for norovirus RNA by reverse transcription quantitative polymerase chain reaction. The times since each patient's last episodes of vomiting and diarrhea were recorded. Size-separating aerosol particle collection was performed.
RESULTS
Norovirus RNA was found in 21 (24%) of 86 air samples from 10 different patients. Only air samples during outbreaks, or before a succeeding outbreak, tested positive for norovirus RNA. Airborne norovirus RNA was also strongly associated with a shorter time period since the last vomiting episode (odds ratio 8.1; P = .04 within 3 hours since the last vomiting episode). The concentrations of airborne norovirus ranged from 5-215 copies/m3, and detectable amounts of norovirus RNA were found in particles <0.95 µm and >4.51 µm.
CONCLUSIONS
The results suggest that recent vomiting is the major source of airborne norovirus and imply a connection between airborne norovirus and outbreaks. The presence of norovirus RNA in submicrometre particles indicates that airborne transmission can be an important transmission route.
Topics: Caliciviridae Infections; Disease Outbreaks; Gastroenteritis; Hospitals; Humans; Norovirus
PubMed: 31257413
DOI: 10.1093/cid/ciz584 -
Discovery Medicine Jul 2010Noroviruses are the leading cause of foodborne disease outbreaks worldwide, and may soon eclipse rotaviruses as the most common cause of severe pediatric... (Review)
Review
Noroviruses are the leading cause of foodborne disease outbreaks worldwide, and may soon eclipse rotaviruses as the most common cause of severe pediatric gastroenteritis, as the use of rotavirus vaccines becomes more widespread. Genetic mutations and recombinations contribute to the broad heterogeneity of noroviruses and the emergence of new epidemic strains. Although typically a self-limited disease, norovirus gastroenteritis can cause significant morbidity and mortality among children, the elderly, and the immunocompromised. The lack of a cell culture or small animal model has hindered norovirus research and the development of novel therapeutic and preventative interventions. However, vaccines based on norovirus capsid protein virus-like particles are promising and may one day become widely available through transgenic expression in plants.
Topics: Gastroenteritis; Genetic Predisposition to Disease; Genetic Variation; Humans; Infection Control; Norovirus
PubMed: 20670600
DOI: No ID Found -
Annals of Laboratory Medicine Jan 2023Reference materials are essential for the quality assurance of molecular detection methods. We developed and characterized synthetic norovirus GI and GII RNA reference...
BACKGROUND
Reference materials are essential for the quality assurance of molecular detection methods. We developed and characterized synthetic norovirus GI and GII RNA reference materials.
METHODS
Norovirus GI and GII RNA sequences including the ORF1-ORF2 junction region were designed based on 1,495 reported norovirus sequences and synthesized via plasmid preparation and transcription. The synthetic norovirus GI and GII RNAs were evaluated using six commercial norovirus detection kits used in Korea and subjected to homogeneity and stability analyses. A multicenter study involving five laboratories and using four commercial real-time PCR norovirus detection assays was conducted for synthetic norovirus RNA characterization and uncertainty measurements.
RESULTS
The synthetic norovirus GI and GII RNAs were positively detected using the six commercial norovirus detection kits and were homogeneous and stable for one year when stored at -20°C or -70°C. All data from the five laboratories were within a range of 1.0 log copies/μL difference for each RNA, and the overall mean concentrations for norovirus GI and GII RNAs were 7.90 log copies/μL and 6.96 log copies/μL, respectively.
CONCLUSIONS
The synthetic norovirus GI and GII RNAs are adequate for quality control based on commercial molecular detection reagents for noroviruses with high sequence variability. The synthetic RNAs can be used as reference materials in norovirus molecular detection methods.
Topics: Caliciviridae Infections; Genotype; Humans; Norovirus; RNA, Viral; Real-Time Polymerase Chain Reaction; Republic of Korea
PubMed: 36045055
DOI: 10.3343/alm.2023.43.1.38 -
Revista Da Associacao Medica Brasileira... 2011Although noroviruses (NoVs) were the first viral agents linked to gastrointestinal disease, for a long time they have been considered secondary cause of gastroenteritis,... (Review)
Review
Although noroviruses (NoVs) were the first viral agents linked to gastrointestinal disease, for a long time they have been considered secondary cause of gastroenteritis, second to rotaviruses as etiologic agents. The development of molecular techniques in diagnosing NoV provided a clearer insight into the epidemiological impact of these viruses, which are currently recognized not only as the leading cause of non-bacterial gastroenteritis outbreaks, but also as a major cause of sporadic gastroenteritis in both children and adults. This review focuses on the required knowledge to understand their morphology, genetics, transmission, pathogenesis, and control. Since no vaccine is available, prevention of NoV infection relies mainly on strict community and personal hygiene measures.
Topics: Caliciviridae Infections; Diarrhea; Gastroenteritis; Humans; Norovirus
PubMed: 21876931
DOI: 10.1590/s0104-42302011000400023 -
Applied and Environmental Microbiology Aug 2004The viruses most commonly associated with food- and waterborne outbreaks of gastroenteritis are the noroviruses. The lack of a culture method for noroviruses warrants...
The viruses most commonly associated with food- and waterborne outbreaks of gastroenteritis are the noroviruses. The lack of a culture method for noroviruses warrants the use of cultivable model viruses to gain more insight on their transmission routes and inactivation methods. We studied the inactivation of the reported enteric canine calicivirus no. 48 (CaCV) and the respiratory feline calicivirus F9 (FeCV) and correlated inactivation to reduction in PCR units of FeCV, CaCV, and a norovirus. Inactivation of suspended viruses was temperature and time dependent in the range from 0 to 100 degrees C. UV-B radiation from 0 to 150 mJ/cm(2) caused dose-dependent inactivation, with a 3 D (D = 1 log(10)) reduction in infectivity at 34 mJ/cm(2) for both viruses. Inactivation by 70% ethanol was inefficient, with only 3 D reduction after 30 min. Sodium hypochlorite solutions were only effective at >300 ppm. FeCV showed a higher stability at pH <3 and pH >7 than CaCV. For all treatments, detection of viral RNA underestimated the reduction in viral infectivity. Norovirus was never more sensitive than the animal caliciviruses and profoundly more resistant to low and high pH. Overall, both animal viruses showed similar inactivation profiles when exposed to heat or UV-B radiation or when incubated in ethanol or hypochlorite. The low stability of CaCV at low pH suggests that this is not a typical enteric (calici-) virus. The incomplete inactivation by ethanol and the high hypochlorite concentration needed for sufficient virus inactivation point to a concern for decontamination of fomites and surfaces contaminated with noroviruses and virus-safe water.
Topics: Animals; Caliciviridae; Calicivirus, Feline; Cats; Cell Line; Disinfection; Dogs; Dose-Response Relationship, Radiation; Ethanol; Hot Temperature; Humans; Norovirus; RNA, Viral; Reverse Transcriptase Polymerase Chain Reaction; Sodium Hypochlorite; Ultraviolet Rays
PubMed: 15294783
DOI: 10.1128/AEM.70.8.4538-4543.2004 -
Human Vaccines & Immunotherapeutics Nov 2017Norovirus is the commonest cause of gastrointestinal disease worldwide in. Infections with norovirus occur in all age groups, however, the highest incidence is in...
Norovirus is the commonest cause of gastrointestinal disease worldwide in. Infections with norovirus occur in all age groups, however, the highest incidence is in children aged less than five years. Surveillance of norovirus is complicated because most people do not contact medical services when they are ill. Nevertheless, Public health laboratory surveillance worldwide has demonstrated the dominance of GII.4 viruses in the population. Better epidemiological surveillance and outbreak investigations, coupled with wider implementation of molecular-based laboratory diagnostics are leading to better estimates of the burden of norovirus infections as well as improved outbreak control. Recent advances in cell culture systems for norovirus and current research investigating the distribution of norovirus-associated disease in the population, for whom the disease burden is greatest, understanding host susceptibility factors, and methodologies for ascertaining cases, are important in increasing our understanding of norovirus. The key to surveillance of norovirus is allying the epidemiology with surveillance of virology. With recent advances in laboratory culture systems for norovirus, next generation sequencing technologies, improved diagnostics and measuring phenotypic characteristics of noroviruses, there are new opportunities to advance understanding of this common and important human pathogen that will help design strategies for vaccine and antiviral development, and how these might be best deployed to control norovirus infection.
Topics: Caliciviridae Infections; Child; Child, Preschool; Clinical Laboratory Techniques; Cost of Illness; Disease Outbreaks; Gastroenteritis; Genotype; Humans; Incidence; Infant; Infection Control; Norovirus; Phylogeny; Population Surveillance; Young Adult
PubMed: 28846473
DOI: 10.1080/21645515.2017.1360455