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differentiation and protective capacity of virus-specific cd8+ t cells suggest murine norovirus persistence in an immune-privileged enteric niche.noroviruses can establish chronic infections with active viral shedding in healthy humans but whether persistence is associated with adaptive immune dysfunction is unknown. we used genetically engineered strains of mouse norovirus (mnv) to investigate cd8+ t cell differentiation during chronic infection. we found that chronic infection drove mnv-specific tissue-resident memory (trm) cd8+ t cells to a differentiation state resembling inflationary effector responses against latent cytomegalovirus ...201729031786
norovirus cell tropism is determined by combinatorial action of a viral non-structural protein and host cytokine.cellular tropism during persistent viral infection is commonly conferred by the interaction of a viral surface protein with a host receptor complex. norovirus, the leading global cause of gastroenteritis, can be persistently shed during infection, but its in vivo cellular tropism and tropism determinants remain unidentified. using murine norovirus (mnov), we determine that a small number of intestinal epithelial cells (iecs) serve as the reservoir for fecal shedding and persistence. the viral no ...201728966054
evaluation of air samplers and filter materials for collection and recovery of airborne norovirus.the aim of this study was to identify the most efficient sampling method for quantitative pcr-based detection of airborne human norovirus (nov).201728921812
reduction of human norovirus gi, gii, and surrogates by peracetic acid and monochloramine in municipal secondary wastewater effluent.the objective of this study was to characterize human norovirus (hnov) gi and gii reductions during disinfection by peracetic acid (paa) and monochloramine in secondary wastewater (ww) and phosphate buffer (pb) as assessed by reverse transcription-qpcr (rt-qpcr). infectivity and rt-qpcr reductions are also presented for surrogate viruses murine norovirus (mnv) and bacteriophage ms2 under identical experimental conditions to aid in interpretation of hnov molecular data. in ww, rt-qpcr reductions ...201728910089
application of gamma radiation for the reduction of norovirus and the quality stability in optimally ripened cabbage kimchi.optimally ripened commercial cabbage kimchi is considered the main cause of enteric norovirus (nov) outbreaks in korea. this study investigated the effect of 1-10kgy gamma radiation on the inactivation of murine norovirus-1 (mnv-1; initial inoculum of 5-6log10pfu/ml), used as a human nov surrogate, in kimchi. the effects of gamma radiation on the ph and acidity were also examined to address the index of quality and fermentation, respectively. titers of mnv-1 significantly reduced (p<0.05) in kim ...201728888451
efficacy of ethanol against viruses in hand disinfection.ethanol is used worldwide in healthcare facilities for hand rubbing. it has been reported to have a stronger and broader virucidal activity compared with propanols. the aim of this review was to describe the spectrum of virucidal activity of ethanol in solution or as commercially available products. a systematic search was conducted. studies were selected when they contained original data on reduction of viral infectivity from suspension tests (49 studies) and contaminated hands (17 studies). et ...201728882643
rna sequencing of murine norovirus-infected cells reveals transcriptional alteration of genes important to viral recognition and antigen presentation.viruses inherently exploit normal cellular functions to promote replication and survival. one mechanism involves transcriptional control of the host, and knowledge of the genes modified and their molecular function can aid in understanding viral-host interactions. norovirus pathogenesis, despite the recent advances in cell cultivation, remains largely uncharacterized. several studies have utilized the related murine norovirus (mnv) to identify innate response, antigen presentation, and cellular ...201728848558
inhibition of calcineurin or imp dehydrogenase exerts moderate to potent antiviral activity against norovirus replication.norovirus is a major cause of acute gastroenteritis worldwide and has emerged as an important issue of chronic infection in transplantation patients. since no approved antiviral is available, we evaluated the effects of different immunosuppressants and ribavirin on norovirus and explored their mechanisms of action by using a human norovirus (hunv) replicon-harboring model and a surrogate murine norovirus (mnv) infectious model. the roles of the corresponding drug targets were investigated by gai ...201728807916
identification of amino acids within norovirus polymerase involved in rna binding and viral replication.until recently, molecular studies on human norovirus (hunov), a major causative agent of gastroenteritis, have been hampered by the lack of an efficient cell culture system. murine norovirus-1 (mnv-1) has served as a surrogate model system for norovirus research, due to the availability of robust cell culture systems and reverse genetics. to identify amino acids involved in rna synthesis by the viral rna-dependent rna polymerase (ns7), we constructed ns7 mutants in which basic amino acids surrou ...201728640742
minimizing bias in virally seeded water treatment studies: evaluation of optimal bacteriophage and mammalian virus preparation methodologies.one key assumption impacting data quality in viral inactivation studies is that reduction estimates are not altered by the virus seeding process. however, seeding viruses often involves the inadvertent addition of co-constituents such as cell culture components or additives used during preparation steps which can impact viral reduction estimates by inducing non-representative oxidant demand in disinfection studies and fouling in membrane assessments. the objective of this study was therefore to ...201728616834
comparative inactivation of murine norovirus and ms2 bacteriophage by peracetic acid and monochloramine in municipal secondary wastewater effluent.chlorination has long been used for disinfection of municipal wastewater (mww) effluent while the use peracetic acid (paa) has been proposed more recently in the united states. previous work has demonstrated the bactericidal effectiveness of paa and monochloramine in wastewater, but limited information is available for viruses, especially ones of mammalian origin (e.g., norovirus). therefore, a comparative assessment was performed of the virucidal efficacy of paa and monochloramine against murin ...201728165216
recent advances in understanding noroviruses.noroviruses are the leading cause of acute gastroenteritis around the world. an individual living in the united states is estimated to develop norovirus infection five times in his or her lifetime. despite this, there is currently no antiviral or vaccine to combat the infection, in large part because of the historical lack of cell culture and small animal models. however, the last few years of norovirus research were marked by a number of ground-breaking advances that have overcome technical bar ...201728163914
virucidal efficacy of a sonicated hydrogen peroxide system (trophon® epr) following european and german test methods.aim: the virucidal efficacy of an automated ultrasound probe disinfector (trophon® epr) was evaluated in a three step procedure according to european and german test methods. this system uses sonicated hydrogen peroxide mist (35%) at elevated temperature (50°c) in a closed chamber with control of all parameters within a 7 minute cycle. methods: in the first step of examination, the peroxide solution was tested in a quantitative suspension assay according to the guideline of deutsche vereinigung ...201728149707
transcriptomic analysis of human norovirus ns1-2 protein highlights a multifunctional role in murine monocytes.the gii.4 sydney 2012 strain of human norovirus (hunov) is a pandemic strain that is responsible for the majority of norovirus outbreaks in healthcare settings. the function of the non-structural (ns)1-2 protein from hunov is unknown.201728056773
murine norovirus infection in brazilian animal facilities.murine norovirus (mnv) is a single-stranded positive-sense rna virus of the caliciviridae family. mnv has been reported to infect laboratory mice with the ability to cause lethal infections in strains lacking components of the innate immune response. currently, mnv is considered the most prevalent infectious agent detected in laboratory mouse facilities. in this study, mice in 22 laboratory animal facilities within brazil were analyzed for mnv infection. using primers targeting a conserved regio ...201728049885
hs-afm and sers analysis of murine norovirus infection: involvement of the lipid rafts.studies on human norovirus are severely hampered by the absence of a cell culture system until the discovery of murine norovirus (mnv). the cell membrane domains called lipid rafts have been defined as a port of entry for viruses. this study is conducted to investigate murine norovirus binding on the mouse leukemic monocyte macrophage cell line. lipid raft related structures are extracted from cells by detergent treatment resulting detergent-resistant membrane (drms) domains. the real-time polym ...201728044439
nonthermal inactivation of norovirus surrogates on blueberries using atmospheric cold plasma.viruses are currently the leading cause of foodborne outbreaks, most of which are associated with foods consumed raw. cold plasma (cp) is an emerging novel nonthermal technology that can be used to surface decontaminate foods. this study investigated cp technology for the nonthermal inactivation of human norovirus surrogates, tulane virus (tv) and murine norovirus (mnv), on the surface of blueberries. blueberries (5 g) were weighed into sterile 4 oz. glass jars and inoculated with tv, 5 log pfu/ ...201728040155
high-throughput sequencing analysis reveals the genetic diversity of different regions of the murine norovirus genome during in vitro replication.in this study, we report the genetic diversity and nucleotide mutation rates of five representative regions of the murine norovirus genome during in vitro passages. the mutation rates were similar in genomic regions encompassing partial coding sequences for non-structural (ns) 1-2, ns5, ns6, ns7 proteins within open reading frame (orf) 1. in a region encoding a portion of the major capsid protein (vp1) within orf2 (also including the orf4 region) and a portion of the minor structural protein (vp ...201727942973
the effect of heat and free chlorine treatments on the surface properties of murine norovirus.heat and free chlorine are among the most efficient and commonly used treatments to inactivate enteric viruses, but their global inactivation mechanisms have not been elucidated yet. these treatments have been shown to affect at least the capsid proteins of viruses and thus may affect the surface properties (i.e. electrostatic charge and hydrophobicity) of such particles. our aim was to study the effects of heat and free chlorine on surface properties for a murine norovirus chosen as surrogate f ...201727888443
high hydrostatic pressure inactivation of murine norovirus and human noroviruses on green onions and in salsa.in this study, high hydrostatic pressure (hhp) was evaluated as an intervention for human noroviruses (hunovs) in green onions and salsa. to determine the effect of water during hhp treatment on virus inactivation, a hunov surrogate, murine norovirus 1 (mnv-1), was inoculated onto green onions and then hhp-treated at 350mpa with or without water at 4 or 20°c. the presence of water enhanced hhp inactivation of mnv-1 on green onions at 4°c but not at 20°c. to test the temperature effect on hhp ina ...201727846447
norovirus polymerase fidelity contributes to viral transmission in vivo.intrahost genetic diversity and replication error rates are intricately linked to rna virus pathogenesis, with alterations in viral polymerase fidelity typically leading to attenuation during infections in vivo. we have previously shown that norovirus intrahost genetic diversity also influences viral pathogenesis using the murine norovirus model, as increasing viral mutation frequency using a mutagenic nucleoside resulted in clearance of a persistent infection in mice. given the role of replicat ...201727777985
membrane alterations induced by nonstructural proteins of human norovirus.human noroviruses (hunov) are the most frequent cause of non-bacterial acute gastroenteritis worldwide, particularly genogroup ii genotype 4 (gii.4) variants. the viral nonstructural (ns) proteins encoded by the orf1 polyprotein induce vesical clusters harboring the viral replication sites. little is known so far about the ultrastructure of these replication organelles or the contribution of individual ns proteins to their biogenesis. we compared the ultrastructural changes induced by expression ...201729077760
norovirus escape from broadly neutralizing antibodies is limited to allostery-like mechanisms.ideal antiviral vaccines elicit antibodies (abs) with broad strain recognition that bind to regions that are difficult to mutate for escape. using 10 murine norovirus (mnv) strains and 5 human norovirus (hunov) virus-like particles (vlps), we identified monoclonal antibody (mab) 2d3, which broadly neutralized all mnv strains tested. importantly, escape mutants corresponding to this antibody were very slow to develop and were distal to those raised against our previously studied antibody, a6.2. t ...201729062895
assessment of the efficacy of membrane filtration processes to remove human enteric viruses and the suitability of bacteriophages and a plant virus as surrogates for those viruses.here, we evaluated the efficacy of direct microfiltration (mf) and ultrafiltration (uf) to remove three representative human enteric viruses (i.e., adenovirus [adv] type 40, coxsackievirus [cv] b5, and hepatitis a virus [hav] ib), and one surrogate of human caliciviruses (i.e., murine norovirus [mnv] type 1). eight different mf membranes and three different uf membranes were used. we also examined the ability of coagulation pretreatment with high-basicity polyaluminum chloride (pacl) to enhance ...201728259077
blueberry proanthocyanidins against human norovirus surrogates in model foods and under simulated gastric conditions.blueberry proanthocyanidins (b-pac) are known to decrease titers of human norovirus surrogates in vitro. the application of b-pac as therapeutic or preventive options against foodborne viral illness needs to be determined using model foods and simulated gastric conditions in vitro. the objective of this study was to evaluate the antiviral effect of b-pac in model foods (apple juice (aj) and 2% reduced fat milk) and simulated gastrointestinal fluids against cultivable human norovirus surrogates ( ...201728040178
antiviral effect of theaflavins against caliciviruses.caliciviruses are contagious pathogens of humans and various animals. they are the most common cause of viral gastroenteritis in humans, and can cause lethal diseases in domestic animals such as cats, rabbits and immunocompromised mice. in this study, we conducted cytopathic effect-based screening of 2080 selected compounds from our in-house library to find antiviral compounds against three culturable caliciviruses: feline calicivirus, murine norovirus (mnv) and porcine sapovirus (posav). we ide ...201727756911
inhibition of murine norovirus and feline calicivirus by edible herbal extracts.human noroviruses (hunovs) cause foodborne and waterborne viral gastroenteritis worldwide. because hunov culture systems have not been developed thus far, no available medicines or vaccines preventing infection with hunovs exist. some herbal extracts were considered as phytomedicines because of their bioactive components. in this study, the inhibitory effects of 29 edible herbal extracts against the norovirus surrogates murine norovirus (mnv) and feline calicivirus (fcv) were examined. fcv was s ...201727807684
inactivation of viruses and bacteriophages as models for swine hepatitis e virus in food matrices.hepatitis e virus has been recognised as a food-borne virus hazard in pork products, due to its zoonotic properties. this risk can be reduced by adequate treatment of the food to inactivate food-borne viruses. we used a spectrum of viruses and bacteriophages to evaluate the effect of three food treatments: high pressure processing (hpp), lactic acid (la) and intense light pulse (ilp) treatments. on swine liver at 400 mpa for 10 min, hpp gave log10 reductions of ≥4.2, ≥5.0 and 3.4 for feline cali ...201727783334
elimination of representative contaminant candidate list viruses, coxsackievirus, echovirus, hepatitis a virus, and norovirus, from water by coagulation processes.we examined the removal of representative contaminant candidate list (ccl) viruses (coxsackievirus [cv] b5, echovirus type [ev] 11, and hepatitis a virus [hav] ib), recombinant norovirus virus-like particles (rnv-vlps), and murine norovirus (mnv) type 1 by coagulation. water samples were subjected to coagulation with polyaluminum chloride (pacl, basicity 1.5) followed by either settling or settling and filtration. together with our previously published results, the removal ratio order, as evalua ...201728011355
virucidal efficacy of food additive grade calcium hydroxide against surrogate of human norovirus.an alkaline agent, namely, food additive grade calcium hydroxide (fdca(oh)2) in the solution, powder and suspension forms was evaluated as a virucidal agent, using a murine norovirus (mnv) as the surrogate for human norovirus. the main constituent of fdca(oh)2 is ca(oh)2, which has ph 13 in 0.17% solution. the results showed that 0.17% fdca(oh)2 solution could inactivate mnv within 30s even in the presence of organic materials (5% fetal bovine serum (fbs)). in a contaminated surface experiment, ...201829054741
comparative transcriptomic response of primary and immortalized macrophages to murine norovirus infection.murine norovirus (nov) is genetically similar to human nov and offers both an efficient in vitro cell culture system and an animal model by which to investigate the molecular basis of replication. in this study, we present a detailed global view of host alterations to cellular pathways that occur during the progression of a nov infection. this was accomplished for both mus musculus balb/c-derived raw264.7 (raw) cells, an immortalized cell line widely used in in vitro replication studies, and pri ...201829735480
interferon lambda (ifn-λ) efficiently blocks norovirus transmission in a mouse model.human noroviruses are highly efficient in person to person transmission thus associated with explosive outbreaks of acute gastroenteritis. outbreak control is limited to disinfection and isolation measures. strategies to control the spread of noroviruses should be developed and models to study norovirus transmission will greatly facilitate this. here, a mouse-to-mouse transmission model, in which mice develop acute murine norovirus (mnv)-induced diarrhea, was used to explore the role of interfer ...201829080649
evaluation of the suitability of a plant virus, pepper mild mottle virus, as a surrogate of human enteric viruses for assessment of the efficacy of coagulation-rapid sand filtration to remove those viruses.here, we evaluated the removal of three representative human enteric viruses - adenovirus (adv) type 40, coxsackievirus (cv) b5, and hepatitis a virus (hav) ib - and one surrogate of human caliciviruses - murine norovirus (mnv) type 1 - by coagulation-rapid sand filtration, using water samples from eight water sources for drinking water treatment plants in japan. the removal ratios of a plant virus (pepper mild mottle virus; pmmov) and two bacteriophages (ms2 and φx174) were compared with the re ...201829182907
alcohols as surface disinfectants in healthcare settings.isopropyl alcohol and ethyl alcohol have been used as low-level disinfectants in healthcare settings for many years. recent studies have found that ethyl alcohol inhibits protein synthesis in escherichia coli by direct effects on ribosomes and rna polymerase and that 60%-70% solutions have in vitro efficacy against murine norovirus, ebola virus, and several coronaviruses. alcohol prep pads or towelettes containing isopropyl or ethyl alcohol and water have been used primarily for disinfection of ...201829374503
testing for human norovirus and recovery of process control in outbreak-associated produce items.the development of rapid and sensitive detection methods for human noroviruses (hunov) in produce items is critical, especially with the recent rise in outbreaks associated with this food commodity. in this study, 50-g portions of various produce items linked to a norovirus outbreak (celery, cucumber, lettuce, grapes, and radish) were artificially inoculated with murine norovirus (mnv-1) and concentrated either by ultracentrifugation or polyethylene glycol (peg) precipitation after elution with ...201829280676
inactivation of murine norovirus and hepatitis a virus on fresh raspberries by gaseous ozone treatment.raspberries are vulnerable products for which industrial treatment solutions ensuring both food safety and sensory quality are not easily applicable. raspberries have been associated with numerous foodborne outbreaks in recent decades. ozone has been proven effective as a drinking water treatment against pathogenic microorganisms. nevertheless, to date, little information is available regarding the effect of gaseous ozone on viruses in food matrices. a comparison of the effect of gaseous ozone o ...201829173615
common vole (microtus arvalis) and bank vole (myodes glareolus) derived permanent cell lines differ in their susceptibility and replication kinetics of animal and zoonotic viruses.pathogenesis and reservoir host adaptation of animal and zoonotic viruses are poorly understood due to missing adequate cell culture and animal models. the bank vole (myodes glareolus) and common vole (microtus arvalis) serve as hosts for a variety of zoonotic pathogens. for a better understanding of virus association to a putative animal host, we generated two novel cell lines from bank voles of different evolutionary lineages and two common vole cell lines and assayed their susceptibility, rep ...201931513859
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