Publications
| Title | Abstract | Year Filter | PMID(sorted descending) Filter |
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| incorporating social contact data in spatio-temporal models for infectious disease spread. | summaryroutine public health surveillance of notifiable infectious diseases gives rise to weekly counts of reported cases-possibly stratified by region and/or age group. we investigate how an age-structured social contact matrix can be incorporated into a spatio-temporal endemic-epidemic model for infectious disease counts. to illustrate the approach, we analyze the spread of norovirus gastroenteritis over six age groups within the 12 districts of berlin, 2011-2015, using contact data from the p ... | 2016 | 28025182 |
| the norovirus ns3 protein is a dynamic lipid- and microtubule-associated protein involved in viral rna replication. | norovirus (nov) infections are a significant health burden to society, yet the lack of reliable tissue culture systems has hampered the development of appropriate antiviral therapies. here we show that the nov ns3 protein, derived from murine nov (mnv), is intimately associated with the mnv replication complex and the viral replication intermediate double-stranded rna (dsrna). we observed that when expressed individually, mnv ns3 and ns3 encoded by human norwalk virus (nv) induced the formation ... | 2017 | 27881660 |
| replication of human norovirus rna in mammalian cells reveals lack of interferon response. | human noroviruses (hunovs), named after the prototype strain norwalk virus (nv), are a leading cause of acute gastroenteritis outbreaks worldwide. studies on the related murine norovirus (mnv) have demonstrated the importance of an interferon (ifn) response in host control of virus replication, but this remains unclear for hunovs. despite the lack of an efficient cell culture infection system, transfection of stool-isolated nv rna into mammalian cells leads to viral rna replication and virus pro ... | 2016 | 27466422 |
| frequent use of the iga isotype in human b cells encoding potent norovirus-specific monoclonal antibodies that block hbga binding. | noroviruses (nov) are the most common cause of non-bacterial acute gastroenteritis and cause local outbreaks of illness, especially in confined situations. despite being identified four decades ago, the correlates of protection against norovirus gastroenteritis are still being elucidated. recent studies have shown an association of protection with nov-specific serum histo-blood group antigen-blocking antibody and with serum iga in patients vaccinated with nov vlps. here, we describe the isolatio ... | 2016 | 27355511 |
| natural norovirus infections in rhesus macaques. | using a recently developed real-time reverse transcription pcr, i retested 500 fecal samples from rhesus macaques collected in 2008. previous conventional reverse transcription pcr testing identified 1 isolate of gii norovirus; retesting found gi, gii, and possible giv noroviruses in the samples, indicating the natural circulation of noroviruses in nonhuman primate colonies. | 2016 | 27314565 |
| vomiting as a symptom and transmission risk in norovirus illness: evidence from human challenge studies. | in the us, noroviruses are estimated to cause 21 million cases annually with economic losses reaching $2 billion. outbreak investigations frequently implicate vomiting as a major transmission risk. however, little is known about the characteristics of vomiting as a symptom or the amount of virus present in emesis. | 2016 | 27116105 |
| an examination of co-infection in acute gastroenteritis and histo-blood group antigens leading to viral infection susceptibility. | the aim of the present study was to evaluate co-infection in the gastrointestinal tract in terms of viruses, bacteria and the abo blood group. we hypothesized that a combination of norovirus (nv) and bacteria in the gastrointestinal tract could affect the likelihood of an individual to contracting nv. histo-blood group antigens (hbgas) are considered to act as receptors that can lead to nv susceptibility. in addition to genetics, co-infection in the gastrointestinal tract may be associated with ... | 2016 | 26998270 |
| mapping and modeling of a strain-specific epitope in the norwalk virus capsid inner shell. | noroviruses are diverse positive-strand rna viruses associated with acute gastroenteritis. cross-reactive epitopes have been mapped primarily to conserved sequences in the capsid vp1 shell (s) domain, and strain-specific epitopes to the highly variable protruding (p) domain. in this work, we investigated a strain-specific linear epitope defined by mab nv10 that was raised against prototype (genogroup i.1) strain norwalk virus (nv). using peptide scanning and mutagenesis, the epitope was mapped t ... | 2016 | 26971245 |
| 5' and 3' untranslated regions strongly enhance performance of geminiviral replicons in nicotiana benthamiana leaves. | we previously reported a recombinant protein production system based on a geminivirus replicon that yields high levels of vaccine antigens and monoclonal antibodies in plants. the bean yellow dwarf virus (beydv) replicon generates massive amounts of dna copies, which engage the plant transcription machinery. however, we noticed a disparity between transcript level and protein production, suggesting that mrnas could be more efficiently utilized. in this study, we systematically evaluated genetic ... | 2016 | 26941764 |
| antiviral activity of gold/copper sulfide core/shell nanoparticles against human norovirus virus-like particles. | human norovirus is a leading cause of acute gastroenteritis worldwide in a plethora of residential and commercial settings, including restaurants, schools, and hospitals. methods for easily detecting the virus and for treating and preventing infection are critical to stopping norovirus outbreaks, and inactivation via nanoparticles (nps) is a more universal and attractive alternative to other physical and chemical approaches. using norovirus gi.1 (norwalk) virus-like particles (vlps) as a model v ... | 2015 | 26474396 |
| stability of norwalk virus capsid protein interfaces evaluated by in silico nanoindentation. | norwalk virus causes severe gastroenteritis for which there is currently no specific anti-viral therapy. a stage of the infection process is uncoating of the protein capsid to expose the viral genome and allow for viral replication. a mechanical characterization of the norwalk virus may provide important information relating to the mechanism of uncoating. the mechanical strength of the norwalk virus has previously been investigated using atomic force microscopy (afm) nanoindentation experiments. ... | 2015 | 26284238 |
| serum immunoglobulin a cross-strain blockade of human noroviruses. | background. human noroviruses are the leading cause of acute viral gastroenteritis, justifying vaccine development despite a limited understanding of strain immunity. after genogroup i (gi).1 norovirus infection and immunization, blockade antibody titers to multiple virus-like particles (vlps) increase, suggesting that gi cross-protection may occur. methods. immunoglobulin (ig)a was purified from sera collected from gi.1-infected participants, and potential neutralization activity was measured ... | 2015 | 26180833 |
| immunogenicity of newcastle disease virus vectors expressing norwalk virus capsid protein in the presence or absence of vp2 protein. | noroviruses are the most common cause of acute gastroenteritis in humans. development of an effective vaccine is required for reducing their outbreaks. in order to develop a gi norovirus vaccine, newcastle disease virus vectors, rlasota and modified rbc, were used to express vp1 protein of norwalk virus. co-expression of vp1 and vp2 proteins by newcastle disease virus vectors resulted in enhanced expression of norwalk virus vp1 protein and self-assembly of vp1 protein into virus-like particles. ... | 2015 | 26099695 |
| tulane virus as a potential surrogate to mimic norovirus behavior in oysters. | oyster contamination by noroviruses is an important health and economic problem. the present study aimed to compare the behaviors of norwalk virus (the prototype genogroup i norovirus) and two culturable viruses: tulane virus and mengovirus. after bioaccumulation, tissue distributions were quite similar for norwalk virus and tulane virus, with the majority of viral particles detected in digestive tissues, while mengovirus was detected in large amounts in the gills and mantle as well as in digest ... | 2015 | 26025893 |
| application of salivary antibody immunoassays for the detection of incident infections with norwalk virus in a group of volunteers. | norovirus infection is the most common cause of acute gastroenteritis in developed countries. developing an assay based on a non-invasive biomarker for detecting incident norovirus infections could improve disease surveillance and epidemiological investigations. this project involved analysis of iga and igg norovirus-specific antibody responses in saliva samples from a norwalk virus (genogroup i, genotype 1 norovirus) challenge study involving infected and symptomatic, and non-infected asymptoma ... | 2015 | 25985985 |
| antimicrobial activity of bismuth subsalicylate on clostridium difficile, escherichia coli o157:h7, norovirus, and other common enteric pathogens. | previous studies have shown bismuth subsalicylate (bss) has antimicrobial properties, but few studies have addressed the mechanism of action. furthermore, following bss ingestion other bismuth salts form throughout the gastrointestinal tract including bismuth oxychloride (biocl) that also act upon enteric pathogens. to further understand the antimicrobial activity of bismuth in infectious diarrhea, the antimicrobial effect of bss and biocl on clostridium difficile, salmonella, shigella, shiga to ... | 2015 | 25901890 |
| propidium monoazide reverse transcriptase pcr and rt-qpcr for detecting infectious enterovirus and norovirus. | presently there is no established cell line or small animal model that allows for the detection of infectious human norovirus. current methods based on rt-pcr and rt-qpcr detect both infectious and non-infectious virus and thus the conclusions that may be drawn regarding the public health significance of positive findings are limited. in this study, pma rt-pcr and rt-qpcr assays were evaluated for selective detection of infectious poliovirus, murine norovirus (mnv-1), and norwalk virus. viruses ... | 2015 | 25796356 |
| mucosal and cellular immune responses to norwalk virus. | 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. | 2015 | 25635121 |
| crystal structures of gi.8 boxer virus p dimers in complex with hbgas, a novel evolutionary path selected by the lewis epitope. | human noroviruses (hunovs) recognize histo-blood group antigens (hbgas) as attachment factors, in which genogroup (g) i and gii hunovs use distinct binding interfaces. the genetic and evolutionary relationships of gii hunovs under selection by the host hbgas have been well elucidated via a number of structural studies; however, such relationships among gi novs remain less clear due to the fact that the structures of hbga-binding interfaces of only three gi novs with similar binding profiles are ... | 2015 | 25547362 |
| experimental human infection with norwalk virus elicits a surrogate neutralizing antibody response with cross-genogroup activity. | the human noroviruses (novs) are genetically diverse, rapidly evolving rna viruses and are the major cause of epidemic gastroenteritis of humans. serum antibodies that block the interaction of novs and nov viruslike particles (vlps) with host attachment factors are considered surrogate neutralizing antibodies in the absence of cell culture and small-animal replication models for the human novs. a serological assay for nov-blocking antibodies was used to assess the breadth of the heterotypic anti ... | 2015 | 25540269 |
| norovirus dose-response: are currently available data informative enough to determine how susceptible humans are to infection from a single virus? | two forms of single-hit infection dose-response models have previously been developed to assess available data from human feeding trials and estimate the norovirus dose-response relationship. the mechanistic interpretations of these models include strong assumptions that warrant reconsideration: the first study includes an implicit assumption that there is no immunity to norwalk virus among the specific study population, while the recent second study includes assumptions that such immunity could ... | 2015 | 25522208 |
| dna microarray for detection of gastrointestinal viruses. | gastroenteritis is a clinical illness of humans and other animals that is characterized by vomiting and diarrhea and caused by a variety of pathogens, including viruses. an increasing number of viral species have been associated with gastroenteritis or have been found in stool samples as new molecular tools have been developed. in this work, a dna microarray capable in theory of parallel detection of more than 100 viral species was developed and tested. initial validation was done with 10 differ ... | 2014 | 25355758 |
| immunomagnetic separation combined with rt-qpcr for determining the efficacy of disinfectants against human noroviruses. | little is known about the effectiveness of disinfectants against human noroviruses (nov) partially because human nov cannot be routinely cultured in laboratory. the objective of this study was to develop a nov monoclonal antibody-conjugated immunomagnetic separation (ims) procedure combined with real-time reverse transcription polymerase chain reaction (rt-qpcr) assays to study the in vitro efficacy of disinfectants against human nov. monoclonal antibodies against norwalk virus (nv, gi.1) and no ... | 2016 | 25270388 |
| two human challenge studies confirm high infectivity of norwalk virus. | 2015 | 25121553 | |
| small molecule deubiquitinase inhibitors promote macrophage anti-infective capacity. | the global spread of anti-microbial resistance requires urgent attention, and diverse alternative strategies have been suggested to address this public health concern. host-directed immunomodulatory therapies represent one approach that could reduce selection for resistant bacterial strains. recently, the small molecule deubiquitinase inhibitor wp1130 was reported as a potential anti-infective drug against important human food-borne pathogens, notably listeria monocytogenes and noroviruses. util ... | 2014 | 25093325 |
| genetic susceptibility to norovirus gii.3 and gii.4 infections in chinese pediatric diarrheal disease. | noroviruses (novs) are a leading cause of viral diarrhea in young children. secretor status has been confirmed to be linked with norwalk virus (nov gi.1) infection but there is limited information about whether secretor genotypes are associated with pediatric nov epidemic strains in vivo. | 2014 | 25037042 |
| two human challenge studies confirm high infectivity of norwalk virus. | 2014 | 25013128 | |
| development of a gaussia luciferase-based human norovirus protease reporter system: cell type-specific profile of norwalk virus protease precursors and evaluation of inhibitors. | norwalk virus (nv) is the prototype strain of human noroviruses (hunovs), a group of positive-strand rna viruses in the caliciviridae family and the leading cause of epidemic gastroenteritis worldwide. investigation of hunov replication and development of antiviral therapeutics in cell culture remain challenging tasks. here, we present norogluc, a hunov protease reporter system based on a fusion of nv p41 protein with a naturally secreted gaussia luciferase (gluc), linked by the p41/p22 cleavage ... | 2014 | 25008934 |
| the enterovirus protease inhibitor rupintrivir exerts cross-genotypic anti-norovirus activity and clears cells from the norovirus replicon. | potent and safe inhibitors of norovirus replication are needed for the treatment and prophylaxis of norovirus infections. we here report that the in vitro anti-norovirus activity of the protease inhibitor rupintrivir is extended to murine noroviruses and that rupintrivir clears human cells from their norwalk replicon after only two passages of antiviral pressure. in addition, we demonstrate that rupintrivir inhibits the human norovirus (genogroup ii [gii]) protease and further explain the inhibi ... | 2014 | 24890597 |
| chemical derivatives of a small molecule deubiquitinase inhibitor have antiviral activity against several rna viruses. | most antiviral treatment options target the invading pathogen and unavoidably encounter loss of efficacy as the pathogen mutates to overcome replication restrictions. a good strategy for circumventing drug resistance, or for pathogens without treatment options, is to target host cell proteins that are utilized by viruses during infection. the small molecule wp1130 is a selective deubiquitinase inhibitor shown previously to successfully reduce replication of noroviruses and some other rna viruses ... | 2014 | 24722666 |
| helium beam shadowing for high spatial resolution patterning of antibodies on microstructured diagnostic surfaces. | we have developed a technique for the high-resolution, self-aligning, and high-throughput patterning of antibody binding functionality on surfaces by selectively changing the reactivity of protein-coated surfaces in specific regions of a workpiece with a beam of energetic helium particles. the exposed areas are passivated with bovine serum albumin (bsa) and no longer bind the antigen. we demonstrate that patterns can be formed (1) by using a stencil mask with etched openings that forms a pattern ... | 2013 | 24706125 |
| disease course and viral shedding in experimental norwalk virus and snow mountain virus infection. | norovirus is the most common cause of acute infectious gastroenteritis, causing approximately 21 million cases annually in the usa. the virus is highly contagious and resistant to decontamination, making outbreaks difficult to control. to facilitate the development of better control methods, this study characterized the viral shedding patterns in stools from subjects experimentally infected with genogroup i or ii norovirus. viral stool titers were determined by quantitative real-time rt-pcr for ... | 2014 | 24531909 |
| seroepidemiology of norovirus-associated travelers' diarrhea. | noroviruses (novs) are the most common cause of epidemic gastroenteritis, responsible for at least 50% of all gastroenteritis outbreaks worldwide and were recently identified as a leading cause of travelers' diarrhea (td) in us and european travelers to mexico, guatemala, and india. | 2016 | 24383649 |
| tlr7 and 9 agonists are highly effective mucosal adjuvants for norovirus virus-like particle vaccines. | virus-like particles (vlps) are an active area of vaccine research, development and commercialization. mucosal administration of vlps provides an attractive avenue for delivery of vaccines with the potential to produce robust immune responses. nasal and oral delivery routes are particularly intriguing due to differential activation of mucosa-associated lymphoid tissues. we compared both intranasal and oral administration of vlps with a panel of toll-like receptor (tlr) agonists (tlr3, 5, 7, 7/8, ... | 2014 | 24280723 |
| determination of the 50% human infectious dose for norwalk virus. | noroviruses are the most common cause of gastroenteritis in the united states. an understanding of the infectious dose of these viruses is important for risk assessment studies. | 2014 | 24253285 |
| design, synthesis, and bioevaluation of viral 3c and 3c-like protease inhibitors. | a class of tripeptidyl transition state inhibitors containing a p1 glutamine surrogate, a p2 leucine, and a p3 arylalanines, was found to potently inhibit norwalk virus replication in enzyme and cell based assays. an array of warheads, including aldehyde, α-ketoamide, bisulfite adduct, and α-hydroxyphosphonate transition state mimic, was also investigated. tripeptidyls 2 and 6 possess antiviral activities against noroviruses, human rhinovirus, severe acute respiratory syndrome coronavirus, and c ... | 2013 | 24125888 |
| laboratory evidence of norwalk virus contamination on the hands of infected individuals. | human norovirus (nov) outbreak investigations suggest that the hands of infected individuals play an important role in nov transmission. however, there is no experimental evidence documenting the likelihood and degree of nov contamination on hands. as part of a clinical trial designed to evaluate the efficacy of high-pressure processing for norwalk virus (nv) inactivation in oysters, 159 hand rinse samples were collected from 6 infected and 6 uninfected subjects. nv was concentrated from the sam ... | 2013 | 24123733 |
| structural and inhibitor studies of norovirus 3c-like proteases. | noroviruses have a single-stranded, positive sense 7-8kb rna genome, which encodes a polyprotein precursor processed by a virus-encoded 3c-like cysteine protease (3clpro) to generate mature non-structural proteins. because processing of the polyprotein is essential for virus replication, norovirus 3clpro has been targeted for the discovery of anti-norovirus small molecule therapeutics. thus, we performed functional, structural and inhibition studies of norovirus 3clpro with fluorescence resonanc ... | 2013 | 24055466 |
| the viral polymerase inhibitor 2'-c-methylcytidine inhibits norwalk virus replication and protects against norovirus-induced diarrhea and mortality in a mouse model. | human noroviruses are a major cause of food-borne illness, accountable for 50% of all-etiologies outbreaks of acute gastroenteritis (in both developing and developed countries). there is no vaccine or antiviral drug for the prophylaxis or treatment of norovirus-induced gastroenteritis. we recently reported the inhibitory effect of 2'-c-methylcytidine (2cmc), a hepatitis c virus polymerase inhibitor, on the in vitro replication of murine norovirus (mnv). here we evaluated the inhibitory effect of ... | 2013 | 23986582 |
| expression and assembly of norwalk virus-like particles in plants using a viral rna silencing suppressor gene. | binary vector-based transient expression of heterologous proteins in plants is a very attractive strategy due to the short time required for proceeding from planning to expression. however, this expression system is limited by comparatively lower yields due to strong post-transcriptional gene silencing (ptgs) in the host plants. the aim of this study was to optimize a procedure for expression of norovirus virus-like particles (vlps) in plants using a binary vector with co-expression of a ptgs su ... | 2013 | 23925532 |
| unusual self-assembly properties of norovirus newbury2 virus-like particles. | in the caliciviridae family of nonenveloped, positive-stranded rna viruses, noroviruses are major causes of human and animal gastroenteritis worldwide. the norovirus t=3 icosahedral capsid is made of 180 copies of the vp1 protein, as exemplified in the crystal structure of the virus-like particle (vlp) of the human norwalk virus (nv). it was previously shown that the ca 40-nm recombinant nv vlp can be disassembled and reassembled in vitro. here we report on the disassembly and self-assembly prop ... | 2013 | 23871846 |
| development of norwalk virus-specific monoclonal antibodies with therapeutic potential for the treatment of norwalk virus gastroenteritis. | passive immunoprophylaxis or immunotherapy with norovirus-neutralizing monoclonal antibodies (mabs) could be a useful treatment for high-risk populations, including infants and young children, the elderly, and certain patients who are debilitated or immunocompromised. in order to obtain antinorovirus mabs with therapeutic potential, we stimulated a strong adaptive immune response in chimpanzees to the prototype norovirus strain norwalk virus (nv) (genogroup i.1). a combinatorial phage fab displa ... | 2013 | 23785216 |
| infectivity of gi and gii noroviruses established from oyster related outbreaks. | noroviruses (novs) are the major cause of acute epidemic gastroenteritis in industrialized countries. outbreak strains are predominantly genogroup ii (gii) nov, but genogroup i (gi) strains are regularly found in oyster related outbreaks. the prototype norwalk virus (gi), has been shown to have high infectivity in a human challenge study. whether other novs are equally infectious via natural exposure remains to be established. human susceptibility to nov is partly determined by the secretor stat ... | 2013 | 23746803 |
| epidemiology of norovirus gastroenteritis outbreaks in two primary schools in a city in eastern china. | we describe the epidemiology of 2 outbreaks of norovirus (gii) gastroenteritis in elementary schools in a city in eastern china using data from field investigations, pathogen testing, and face-to-face interviews. the transmission shows a point source type. in a case-control study, we identified airborne and person-to-person transmission as the source of the outbreaks. | 2013 | 23663855 |
| lack of norovirus replication and histo-blood group antigen expression in 3-dimensional intestinal epithelial cells. | noroviruses (novs) are a leading cause of gastroenteritis worldwide. an in vitro model for nov replication remains elusive, making study of the virus difficult. a previous study, which used a 3-dimensional (3-d) intestinal model derived from int-407 cells reported nov replication and extensive cytopathic effects (cpe). using the same 3-d model, but with highly purified norwalk virus (nv), we attempted to replicate this study. our results showed no evidence of nv replication by real-time pcr of v ... | 2013 | 23622517 |
| substrate recognition by norovirus polymerase: microsecond molecular dynamics study. | molecular dynamics simulations of complexes between norwalk virus rna dependent rna polymerase and its natural ctp and 2dctp (both containing the o5'-c5'-c4'-o4' sequence of atoms bridging the triphosphate and sugar moiety) or modified coctp (c5'-o5'-c4'-o4'), cocctp (c5'-o5'-c4'-c4'') substrates were produced by means of cuda programmable graphical processing units and the acemd software package. it enabled us to gain microsecond md trajectories clearly showing that similar nucleoside triphosph ... | 2013 | 23619980 |
| identification and characterization of a peptide affinity reagent for detection of noroviruses in clinical samples. | norovirus (nov) is the most common agent of nonbacterial epidemic gastroenteritis and is estimated to cause 21 million cases of the disease in the united states annually. the antigen enzyme-linked immunosorbent assays (elisas) currently available for nov diagnosis detect only certain strains and are approved for use in the united states only in epidemics where nov is suspected. there is a clear need for simpler, more rapid, and more reliable diagnostic tools for the detection of nov. in this stu ... | 2013 | 23554202 |
| epidemiology and evolution of rotaviruses and noroviruses from an archival who global study in children (1976-79) with implications for vaccine design. | prompted by the discovery of new gastrointestinal viruses, the nih, niaid and who investigated the etiology of acute diarrhea that occurred from 1976-1979 in a global cohort of infants and young children. rotaviruses were found to be major pathogens worldwide, whereas the norwalk virus could not be detected using a radioimmunoassay. the aim of this study is to re-evaluate the role and diversity of rotaviruses and noroviruses in the original cohort using more sensitive current technologies. stool ... | 2013 | 23536875 |
| cryo-em structure of a novel calicivirus, tulane virus. | tulane virus (tv) is a newly isolated cultivatable calicivirus that infects juvenile rhesus macaques. here we report a 6.3 å resolution cryo-electron microscopy structure of the tv virion. the tv virion is about 400 å in diameter and consists of a t = 3 icosahedral protein capsid enclosing the rna genome. 180 copies of the major capsid protein vp1 (∼57 kda) are organized into two types of dimers a/b and c/c and form a thin, smooth shell studded with 90 dimeric protrusions. the overall capsid org ... | 2013 | 23533651 |
| norwalk virus minor capsid protein vp2 associates within the vp1 shell domain. | the major capsid protein of norovirus vp1 assembles to form an icosahedral viral particle. despite evidence that the norwalk virus (nv) minor structural protein vp2 is present in infectious virions, the available crystallographic and electron cryomicroscopy structures of nv have not revealed the location of vp2. in this study, we determined that vp1 associates with vp2 at the interior surface of the capsid, specifically with the shell (s) domain of vp1. we mapped the interaction site to amino ac ... | 2013 | 23408637 |
| structural basis of substrate specificity and protease inhibition in norwalk virus. | norwalk virus (nv), the prototype human calicivirus, is the leading cause of nonbacterial acute gastroenteritis. the nv protease cleaves the polyprotein encoded by open reading frame 1 of the viral genome at five nonhomologous sites, releasing six nonstructural proteins that are essential for viral replication. the structural details of how nv protease recognizes multiple substrates are unclear. in our x-ray structure of an nv protease construct, we observed that the c-terminal tail, representin ... | 2013 | 23365454 |
| structural and dynamics characterization of norovirus protease. | norovirus protease is an essential enzyme for proteolytic maturation of norovirus nonstructural proteins and has been implicated as a potential target for antiviral drug development. although x-ray structural studies of the protease give us wealth of structural information including interactions of the protease with its substrate and dimeric overall structure, the role of protein dynamics in the substrate recognition and the biological relevance of the protease dimer remain unclear. here we dete ... | 2013 | 23319456 |
| persistence of norwalk virus, male-specific coliphage, and escherichia coli on stainless steel coupons and in phosphate-buffered saline. | human noroviruses (novs) are a leading cause of acute gastroenteritis and are frequently transmitted by contaminated food, water, hands, and environmental surfaces. little is known about their environmental stability and/or which alternative microorganisms can serve as effective surrogates. to examine whether escherichia coli and male-specific coliphage ms2 can be appropriate surrogates for novs, approximately 6.8 log genomic equivalent copies of norwalk virus (nv), and 6.0 to 6.5 log pfu or cfu ... | 2012 | 23212011 |
| substrate specificity of tulane virus protease. | tulane virus (tv) is a cultivable calicivirus isolated from rhesus monkeys. in this study, we characterized the substrate specificity of tv protease in trans using recombinant proteases and tv polyprotein fragments containing the predicted proteolytic cleavage sites. cleavage products have been obtained from 4 of the 5 fragments containing (573)q-s(574) between the helicase and 3a-like protein, (712)e-a(713) between the 3a-like protein and vpg, (802)e-g(803) between vpg and the protease, and (97 ... | 2013 | 23141588 |
| in silico 3d structure analysis accelerates the solution of a real viral structure and antibodies docking mechanism. | norwalk virus (nov) is responsible for most outbreaks of non-bacterial gastroenteritis. nov is genetically diverse and show antigenically variable. recently, we produced a monoclonal antibody called 5b-18 that reacts broadly with nov genogroup ii (gii). we suspected the 5b-18 binds to a conformational epitope on 3d structure of virion. x-ray crystallography showed us that 5b-18 binds to nov at the p domain, which protrudes from the capsid surface of the virion. however, there seems to be no spac ... | 2012 | 23133439 |
| antibody responses to norovirus genogroup gi.1 and gii.4 proteases in volunteers administered norwalk virus. | an assay was developed to detect antibodies against two norovirus proteases among participants in a norwalk virus (gi.1) challenge study. prechallenge seroprevalence was lower against the protease from the homologous gi.1 virus than against protease from a heterologous gii.4 strain. seroresponses were detected for 14 of 19 (74%) infected persons. | 2012 | 23035177 |
| secretory pathway antagonism by calicivirus homologues of norwalk virus nonstructural protein p22 is restricted to noroviruses. | our previous report that the norwalk virus nonstructural protein p22 is an antagonist of the cellular secretory pathway suggests a new aspect of norovirus/host interaction. to explore conservation of function of this highly divergent calicivirus protein, we examined the effects of p22 homologues from four human and two murine noroviruses, and feline calicivirus on the secretory pathway. | 2012 | 22943503 |
| predicting susceptibility to norovirus gii.4 by use of a challenge model involving humans. | gii.4 is the predominant norovirus genotype worldwide. challenge models involving humans have shown the association of human histo-blood group antigens (hbgas) and susceptibility to infection with norwalk virus (gi.1 norovirus), but the association of hbgas and infection with other noroviruses is based on results of epidemiological studies. we performed the first gii.4 challenge study involving humans and prospectively evaluated the relationship between hbgas and norovirus infection and associat ... | 2012 | 22927452 |
| broad-spectrum antivirals against 3c or 3c-like proteases of picornaviruses, noroviruses, and coronaviruses. | phylogenetic analysis has demonstrated that some positive-sense rna viruses can be classified into the picornavirus-like supercluster, which includes picornaviruses, caliciviruses, and coronaviruses. these viruses possess 3c or 3c-like proteases (3cpro or 3clpro, respectively), which contain a typical chymotrypsin-like fold and a catalytic triad (or dyad) with a cys residue as a nucleophile. the conserved key sites of 3cpro or 3clpro may serve as attractive targets for the design of broad-spectr ... | 2012 | 22915796 |
| antiviral activity of nucleoside analogues against norovirus. | norovirus (nov) is the leading cause of epidemic gastroenteritis worldwide. the lack of a cell culture has significantly hampered the development of effective therapies against human nov. clinically approved nucleoside and non-nucleoside analogues have been used successfully against rna viruses. | 2012 | 22910194 |
| intranasal vaccination with murabutide enhances humoral and mucosal immune responses to a virus-like particle vaccine. | murabutide (mb) is a synthetic immunomodulator recognized by the nucleotide-binding oligomerization domain-containing protein 2 (nod2) receptor on mammalian cells. mb has previously been approved for testing in multiple human clinical trials to determine its value as an antiviral therapeutic, and as an adjuvant for injected vaccines. we have found a new use for this immunomodulator; it functions as a mucosal adjuvant that enhances immunogenicity of virus-like particles (vlp) administered intrana ... | 2012 | 22855691 |
| antiviral activity of a small molecule deubiquitinase inhibitor occurs via induction of the unfolded protein response. | ubiquitin (ub) is a vital regulatory component in various cellular processes, including cellular responses to viral infection. as obligate intracellular pathogens, viruses have the capacity to manipulate the ubiquitin (ub) cycle to their advantage by encoding ub-modifying proteins including deubiquitinases (dubs). however, how cellular dubs modulate specific viral infections, such as norovirus, is poorly understood. to examine the role of dubs during norovirus infection, we used wp1130, a small ... | 2012 | 22792064 |
| intranasal vaccination with an adjuvanted norwalk virus-like particle vaccine elicits antigen-specific b memory responses in human adult volunteers. | noroviruses are the most frequent cause of acute gastroenteritis in humans of all ages. no vaccines are currently available. an intranasally delivered norwalk (nv) virus-like particle (vlp) vaccine was recently shown to be well tolerated, immunogenic and to protect against infection in phase 1 studies. here, we examined b memory (b(m)) responses in volunteers who received the highest dosage levels of the nv-vlp vaccine (50 μg and 100 μg). we measured the frequency of nv-specific igg and iga-secr ... | 2012 | 22710446 |
| persistence and transferability of noroviruses on and between common surfaces and foods. | human noroviruses (hunov) are the leading cause of foodborne disease, and poor personal hygiene practices of infected workers are the most common mode of contamination. the purpose of this study was to characterize the persistence and transferability of representative noroviruses norwalk virus (nv), snow mountain virus (smv), and murine norovirus 1 (mnv-1) on and between solid surfaces and foods. changes in virus concentration on artificially inoculated solid surfaces (stainless steel, ceramic, ... | 2012 | 22564943 |
| immunogenicity and specificity of norovirus consensus gii.4 virus-like particles in monovalent and bivalent vaccine formulations. | noroviruses, a major cause of acute gastroenteritis worldwide, present antigenic diversity that must be considered for the development of an effective vaccine. in this study, we explored approaches to increase the broad reactivity of virus-like particle (vlp) norovirus vaccine candidates. the immunogenicity of a gii.4 "consensus" vlp that was engineered from sequences of three genetically distinct naturally occurring gii.4 strains was examined for its ability to induce cross-reactive immune resp ... | 2012 | 22469864 |
| the stress (of an) epidemic. | we examined the consequences of being exposed to an outbreak of the norwalk virus at a small university. data from 422 undergraduates supported a model in which the experience of symptoms and perceptions of the university's response to the outbreak predicted fear of future contamination. in turn, fear predicted strain and enhanced hygiene practices. results are consistent with a model of disease outbreak as a traumatic stressor, and implications for organizations dealing with disease outbreaks a ... | 2011 | 22281817 |
| characterization and inhibition of norovirus proteases of genogroups i and ii using a fluorescence resonance energy transfer assay. | noroviruses are the major cause of food- or water-borne gastroenteritis outbreaks in humans. the norovirus protease that cleaves a large viral polyprotein to nonstructural proteins is essential for virus replication and an attractive target for antiviral drug development. noroviruses show high genetic diversity with at least five genogroups, gi-gv, of which gi and gii are responsible for the majority of norovirus infections in humans. we cloned and expressed proteases of norwalk virus (gi) and m ... | 2011 | 22200497 |
| serum hemagglutination inhibition activity correlates with protection from gastroenteritis in persons infected with norwalk virus. | a hemagglutination inhibition assay (hai) was developed to assess serum antibody responses following norwalk virus (nv) infection. hai activity increased significantly in individuals experimentally infected with nv (n=18) and correlated with antibody levels measured in a histo-blood group antigen (hbga) blocking assay. pre-challenge hai antibody levels also correlated with protection from the development of gastroenteritis (mann-whitney, p=0.02). hai is another assay suitable for the detection o ... | 2011 | 22190401 |
| Norovirus vaccine against experimental human Norwalk Virus illness. | Noroviruses cause epidemic and sporadic acute gastroenteritis. No vaccine is available to prevent norovirus illness or infection. | 2011 | 22150036 |
| bioprocessing of plant-derived virus-like particles of norwalk virus capsid protein under current good manufacture practice regulations. | despite the success in expressing a variety of subunit vaccine proteins in plants and the recent stride in improving vaccine accumulation levels by transient expression systems, there is still no plant-derived vaccine that has been licensed for human use. the lack of commercial success of plant-made vaccines lies in several technical and regulatory barriers that remain to be overcome. these challenges include the lack of scalable downstream processing procedures, the uncertainty of regulatory co ... | 2011 | 22134876 |
| Prestress strengthens the shell of Norwalk virus nanoparticles. | We investigated the influence of the protruding domain of Norwalk virus-like particles (NVLP) on its overall structural and mechanical stability. Deletion of the protruding domain yields smooth mutant particles and our AFM nanoindentation measurements show a surprisingly altered indentation response of these particles. Notably, the brittle behavior of the NVLP as compared to the plastic behavior of the mutant reveals that the protruding domain drastically changes the capsid's material properties ... | 2011 | 21967663 |
| Potent inhibition of Norwalk virus by cyclic sulfamide derivatives. | A new class of compounds that exhibit anti-norovirus activity in a cell-based system and embody in their structure a cyclosulfamide scaffold has been identified. The structure of the initial hit (compound 2a, ED(50) 4 µM, TD(50) 50 µM) has been prospected by exploiting multiple points of diversity and generating appropriate structure-activity relationships. | 2011 | 21925886 |
| Robust production of virus-like particles and monoclonal antibodies with geminiviral replicon vectors in lettuce. | Pharmaceutical protein production in plants has been greatly promoted by the development of viral-based vectors and transient expression systems. Tobacco and related Nicotiana species are currently the most common host plants for the generation of plant-made pharmaceutical proteins (PMPs). Downstream processing of target PMPs from these plants, however, is hindered by potential technical and regulatory difficulties owing to the presence of high levels of phenolics and toxic alkaloids. Here, we e ... | 2012 | 21883868 |
| Norovirus infectivity in humans and persistence in water. | To examine the long-term infectivity of human norovirus in water, 13 study subjects were challenged at different time points with groundwater spiked with the prototype human norovirus, Norwalk virus. Norwalk virus spiked in groundwater remained infectious after storage at room temperature in the dark for 61 days (the last time point tested). The Norwalk virus-seeded groundwater was stored for 1,266 days and analyzed, after RNase treatment, by reverse transcription-quantitative PCR (RT-qPCR) to d ... | 2011 | 21856841 |
| crystallography of a lewis-binding norovirus, elucidation of strain-specificity to the polymorphic human histo-blood group antigens. | noroviruses, an important cause of acute gastroenteritis in humans, recognize the histo-blood group antigens (hbgas) as host susceptible factors in a strain-specific manner. the crystal structures of the hbga-binding interfaces of two a/b/h-binding noroviruses, the prototype norwalk virus (gi.1) and a predominant gii.4 strain (va387), have been elucidated. in this study we determined the crystal structures of the p domain protein of the first lewis-binding norovirus (va207, gii.9) that has a dis ... | 2011 | 21811409 |
| design, synthesis, and evaluation of inhibitors of norwalk virus 3c protease. | the first series of peptidyl aldehyde inhibitors that incorporate in their structure a glutamine surrogate has been designed and synthesized based on the known substrate specificity of norwalk virus 3c protease. the inhibitory activity of the compounds with the protease and with a norovirus cell-based replicon system was investigated. members of this class of compounds exhibited noteworthy activity both in vitro and in a cell-based replicon system. | 2011 | 21802286 |
| randomized, double-blinded clinical trial for human norovirus inactivation in oysters by high hydrostatic pressure processing. | contamination of oysters with human noroviruses (hunov) constitutes a human health risk and may lead to severe economic losses in the shellfish industry. there is a need to identify a technology that can inactivate hunov in oysters. in this study, we conducted a randomized, double-blinded clinical trial to assess the effect of high hydrostatic pressure processing (hpp) on norwalk virus (hunov genogroup i.1) inactivation in virus-seeded oysters ingested by subjects. forty-four healthy, positive-s ... | 2011 | 21705552 |
| nucleolin interacts with the feline calicivirus 3' untranslated region and the protease-polymerase ns6 and ns7 proteins, playing a role in virus replication. | cellular proteins play many important roles during the life cycle of all viruses. specifically, host cell nucleic acid-binding proteins interact with viral components of positive-stranded rna viruses and regulate viral translation, as well as rna replication. here, we report that nucleolin, a ubiquitous multifunctional nucleolar shuttling phosphoprotein, interacts with the norwalk virus and feline calicivirus (fcv) genomic 3' untranslated regions (utrs). nucleolin can also form a complex in vitr ... | 2011 | 21680514 |
| backbone and side-chain (1)h, (15)n, and (13)c resonance assignments of norwalk virus protease. | norovirus protease cleaves the virus-encoded polyprotein into six mature nonstructural proteins, presenting itself as an essential enzyme for the viral replication as well as an attractive target for the antiviral drug development. a deeper understanding of the structural mechanism of the protease-substrates/inhibitors interactions by means of solution nmr methods would facilitate a rational design of the virus protease inhibitor. we here report the backbone and side-chain resonance assignment o ... | 2011 | 21647610 |
| intranasal delivery of norwalk virus-like particles formulated in an in situ gelling, dry powder vaccine. | the development of a vaccine to prevent norovirus infections has been focused on immunization at a mucosal surface, but has been limited by the low immunogenicity of self-assembling norwalk virus-like particles (nv vlps) delivered enterically or at nasal surfaces. nasal immunization, which offers the advantage of ease of immunization, faces obstacles imposed by the normal process of mucociliary clearance, which limits residence time of applied antigens. herein, we describe the use of a dry powde ... | 2011 | 21640778 |
| common gene therapy viral vectors do not efficiently penetrate sputum from cystic fibrosis patients. | norwalk virus and human papilloma virus, two viruses that infect humans at mucosal surfaces, have been found capable of rapidly penetrating human mucus secretions. viral vectors for gene therapy of cystic fibrosis (cf) must similarly penetrate purulent lung airway mucus (sputum) to deliver dna to airway epithelial cells. however, surprisingly little is known about the rates at which gene delivery vehicles penetrate sputum, including viral vectors used in clinical trials for cf gene therapy. we f ... | 2011 | 21637751 |
| serological responses to experimental norwalk virus infection measured using a quantitative duplex time-resolved fluorescence immunoassay. | a quantitative duplex time-resolved fluorescence assay (delfia) was developed to measure norwalk virus (nv)-specific iga and igg antibodies simultaneously. the duplex assay showed superior performance by detecting seroconversion following experimental nv infection at an earlier time point than a reference total immunogobulin elisa. | 2011 | 21593238 |
| medical microbiology | the caliciviruses are small, nonenveloped rna viruses that have characteristic cup-shaped depressions on a spherical capsid surface; hence their name, which is derived from calyx or chalice. caliciviruses have a distinctive structure, sometimes described as a star of david, and are also distinctive in their size (27 to 35 nm), in having only a single major polypeptide, and in the functions of the single-stranded rna genome. they produce mucocutaneous and respiratory tract lesions in several anim ... | 1996 | 21413349 |
| geminiviral vectors based on bean yellow dwarf virus for production of vaccine antigens and monoclonal antibodies in plants. | expression of recombinant vaccine antigens and monoclonal antibodies using plant viral vectors has developed extensively during the past several years. the approach benefits from high yields of recombinant protein obtained within days after transient delivery of viral vectors to leaves of nicotiana benthamiana, a tobacco relative. modified viral genomes of both rna and dna viruses have been created. geminiviruses such as bean yellow dwarf virus (beydv) have a small, single stranded dna genome th ... | 2011 | 21358270 |
| clinical development of plant-produced recombinant pharmaceuticals: vaccines, antibodies and beyond. | in the last few years, plants have become an increasingly attractive platform for recombinant protein production. this builds on two decades of research, starting with transgenic approaches to develop oral vaccines in which antigens or therapeutics can be delivered in processed plant biomass, and progressing to transient expression approaches whereby high yields of purified targets are administered parenterally. the advantages of plant-based expression systems include high scalability, low upstr ... | 2011 | 21346417 |
| comparative site-directed mutagenesis in the catalytic amino acid triad in calicivirus proteases. | calicivirus proteases cleave the viral precursor polyprotein encoded by open reading frame 1 (orf1) into multiple intermediate and mature proteins. these proteases have conserved histidine (his), glutamic acid (glu) or aspartic acid (asp), and cysteine (cys) residues that are thought to act as a catalytic triad (i.e. general base, acid and nucleophile, respectively). however, is the triad critical for processing the polyprotein? in the present study, we examined these amino acids in viruses repr ... | 2011 | 21204947 |
| spurious polyadenylation of norovirus narita 104 capsid protein mrna in transgenic plants. | noroviruses are members of the family caliciviridae, and cause a highly communicable gastroenteritis in humans. we explored the potential to develop a plant-based vaccine against narita 104 virus, a genogroup ii norovirus. in stably transgenic potato, we obtained very poor expression of narita 104 virus capsid protein (navcp) despite the use of a strong constitutive promoter (dual enhancer 35s) driving the native coding sequence. we identified potentially detrimental sequence motifs that could m ... | 2011 | 21203799 |
| chimpanzees as an animal model for human norovirus infection and vaccine development. | noroviruses are global agents of acute gastroenteritis, but the development of control strategies has been hampered by the absence of a robust animal model. studies in chimpanzees have played a key role in the characterization of several fastidious hepatitis viruses, and we investigated the feasibility of such studies for the noroviruses. seronegative chimpanzees inoculated i.v. with the human norovirus strain norwalk virus (nv) did not show clinical signs of gastroenteritis, but the onset and d ... | 2010 | 21173246 |
| biodegradable nanogels for oral delivery of interferon for norovirus infection. | norwalk virus (nv) replicon-harboring cells have provided an excellent tool to the development of antivirals. previously we demonstrated that the expression levels of replicon rna and proteins were significantly reduced in the presence of various interferons (ifns) including ifn-α and ifn-γ in a dose-dependent manner in the nv replicon-harboring cells, and suggested that ifns could be therapeutic options for norovirus infection. it was also demonstrated that innate immunity including ifns is cru ... | 2010 | 21144866 |
| individualizing a capstone project: a cruise ship nurse creates a brochure about the norwalk virus. | an ms capstone is a summative academic project where the student is expected to combine personal experience, previous nursing knowledge, and newly acquired graduate nursing skills and integrate them into practice. the authors discuss the challenges of a capstone project from the committee chair and student perspectives. this family nurse practitioner student was a cruise ship nurse who identified a need related to the norwalk virus. the committee chair needed to direct the student through the ca ... | 2011 | 21135680 |
| binding of virus-like particles of norwalk virus to romaine lettuce veins. | noroviruses (nov) annually cause millions of cases of gastrointestinal disease in the united states. nov are associated with raw shellfish outbreaks, particularly oysters, which are thought to bioaccumulate nov particles during the filter-feeding process. nov outbreaks, however, have also been known to occur from other common-source food-borne vehicles, such as lettuce, frozen raspberries, and salad. in this study, we evaluated romaine lettuce as a potential vehicle for nov transmission by testi ... | 2010 | 21037300 |
| adjuvanted intranasal norwalk virus-like particle vaccine elicits antibodies and antibody-secreting cells that express homing receptors for mucosal and peripheral lymphoid tissues. | noroviruses cause significant morbidity and mortality from acute gastroenteritis in all age groups worldwide. | 2010 | 20979455 |
| inhibition of cellular protein secretion by norwalk virus nonstructural protein p22 requires a mimic of an endoplasmic reticulum export signal. | protein trafficking between the endoplasmic reticulum (er) and golgi apparatus is central to cellular homeostasis. er export signals are utilized by a subset of proteins to rapidly exit the er by direct uptake into copii vesicles for transport to the golgi. norwalk virus nonstructural protein p22 contains a yxφesdg motif that mimics a di-acidic er export signal in both sequence and function. however, unlike normal er export signals, the er export signal mimic of p22 is necessary for apparent inh ... | 2010 | 20976190 |
| an intranasally delivered toll-like receptor 7 agonist elicits robust systemic and mucosal responses to norwalk virus-like particles. | norwalk virus (nv) is an enteric pathogen from the genus norovirus and a major cause of nonbacterial gastroenteritis in humans. nv virus-like particles (vlps) are known to elicit systemic and mucosal immune responses when delivered nasally; however, the correlates of immune protection are unknown, and codelivery with a safe and immunogenic mucosal adjuvant may enhance protective anti-nv immune responses. resiquimod (r848), an imidazoquinoline-based toll-like receptor 7 and/or 8 (tlr7/8) agonist, ... | 2010 | 20962211 |
| measuring quality of mental health care: a review of initiatives and programs in selected countries. | this review article presents a systematic review of grey literature describing current initiatives that assess the quality of mental health care in 12 countries, as collected by the international initiative for mental health leadership.there have been increased efforts in many countries to develop and implement mental health indicator schemes to measure and monitor the quality of mental health care at the national and subnational level. most mental health indicator sets are part of larger health ... | 2010 | 20840801 |
| serological correlate of protection against norovirus-induced gastroenteritis. | norovirus infection is the leading cause of acute nonbacterial gastroenteritis. histoblood group antigens (hbgas) are host susceptibility determinants for norwalk virus (nv) infection. we hypothesized that antibodies that block nv-hbga binding are associated with protection from clinical illness following nv exposure. | 2010 | 20815703 |
| sibling-size variation in brown trout salmo trutta in relation to egg size and stream size. | sibling-size variation (ssv), estimated as the coefficient of variation of egg size, was investigated for 13 populations of brown trout salmo trutta. ssv was negatively correlated with mean egg size both at the population and individual levels. after correction for the effect of mean egg size, ssv was also negatively correlated with stream size. these results provide new information about how salmonid ssv can vary at different ecological scales (individual, population and region). the results ar ... | 2009 | 20735629 |
| norwalk virus does not replicate in human macrophages or dendritic cells derived from the peripheral blood of susceptible humans. | human noroviruses are difficult to study due to the lack of an efficient in vitro cell culture system or small animal model. murine norovirus replicates in murine macrophages (mphi) and dendritic cells (dcs), raising the possibility that human novs might replicate in such human cell types. to test this hypothesis, we evaluated dcs and mphi derived from monocyte subsets and cd11c(+) dcs isolated from peripheral blood mononuclear cells of individuals susceptible to norwalk virus (nv) infection. th ... | 2010 | 20667573 |
| quantification of norwalk virus inocula: comparison of endpoint titration and real-time reverse transcription-pcr methods. | human noroviruses (nov) are the leading cause of epidemic acute gastroenteritis. in order to fully characterize features such as persistence and infectious dose, precise quantification of virus concentration is necessary. the purpose of this study was to compare two methods [endpoint titration rt-pcr and quantitative rt-pcr (rt-qpcr)] with respect to quantification of norwalk virus (nv) in inocula made from purified stock suspensions of human fecal specimens. a full-length nv rna transcript was ... | 2010 | 20648618 |
| identification of cross-reactive norovirus cd4+ t cell epitopes. | immune responses and the components of protective immunity following norovirus infection in humans are poorly understood. although antibody responses following norovirus infection have been partially characterized, t cell responses in humans remain largely undefined. in contrast, t cells have been shown to be essential for viral clearance of mouse norovirus (mnv) infection. in this paper, we demonstrate that cd4(+) t cells secrete gamma interferon (ifn-gamma) in response to stimulation with mnv ... | 2010 | 20573810 |