RESUMEN
Norovirus (NoV) is the leading cause of acute gastroenteritis (AGE) in many countries that have introduced universal rotavirus mass vaccination. This is the first study to report data on NoV strains in Estonia. We recruited 2249 children aged 0-18 years hospitalized for AGE in Estonian hospitals from February 1, 2015 to August 31, 2016. Norovirus gastroenteritis (NoVGE) was diagnosed in 14.5% (n = 325) cases. Stool sample for RNA extraction and genotyping was available in 86% (n = 280) of NoVGE cases (2015, n = 91; 2016, n = 189). Dominant capsid types detected in 75% (n = 210) samples were, GII.4 (63.8%, n = 134), GII.3 (15.2%, n = 32), GII.17 (6.7%, n = 14), and GII.6 (5.2%, n = 11). Prevailing RNA polymerase types found in 77% (n = 215) samples were GII.P31 (51.1%, n = 110), GII.P21 (17.7%, n = 38), GII.P4 (11.2%, n = 24), and GII.P7 (6.5%, n = 14). Both regions were typeable for 67% (n = 189) of samples. Most prevalent strains were GII.4Sydney_2012[P31] (48.7%, n = 92), GII.3[P21] (15.3%, n = 29), GII.4Sydney_2012[P4] (5.8%, n = 11) and GII.17[P17] (5.8%, n = 11). Simpson's diversity index showed a significant difference between the age groups 1-4 and 5-9 years: D 0.64 (95% confidence interval [CI]: 0.55-0.73) versus 0.83 (95% CI: 0.81-0.86), respectively (p = 0.03). An accurate understanding of NoV strain diversity is important for control and preventive measures, especially in the postrotavirus vaccine era.
Asunto(s)
Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Virus Norwalk , Niño , Estonia/epidemiología , Heces , Gastroenteritis/epidemiología , Genotipo , Humanos , Norovirus/genética , Filogenia , PrevalenciaRESUMEN
BACKGROUND: The role of histo-blood group on the burden and severity of norovirus gastroenteritis in young infants has not been well documented. METHODS: Norovirus gastroenteritis was assessed in 443 Nicaraguan children followed from birth until 3 years of age. Stool samples were tested for norovirus by reverse-transcription quantitative polymerase chain reaction (RT-qPCR), and histo-blood group antigens (HBGAs) were determined by phenotyping of saliva and blood. Hazard ratios and predictors of norovirus acute gastroenteritis (AGE) outcome stratified by HBGA were estimated using Cox proportional hazards models. RESULTS: Of 1353 AGE episodes experienced by children, 229 (17%) tested positive for norovirus with an overall incidence of 21.9/100 child-years. Secretor children were infected as early as 2 months of age and had a higher incidence of norovirus GII compared to nonsecretor children (15.4 vs 4.1/100 child-years, P = .006). Furthermore, all GII.4 AGE episodes occurred in secretor children. Children infected with GI (adjusted odds ratio [aOR], 0.09 [95% confidence interval {CI}, .02-.33]) or non-GII.4 viruses (aOR, 0.2 [95% CI, .07-.6]) were less likely to have severe AGE compared to GII.4-infected children. CONCLUSIONS: Secretor status in children strongly influences the incidence of symptomatic norovirus infection in a genogroup or genotype-dependent manner and provides evidence that clinical severity in children depends on norovirus genotypes.
Asunto(s)
Antígenos de Grupos Sanguíneos , Infecciones por Caliciviridae/epidemiología , Heces/virología , Norovirus/aislamiento & purificación , Saliva/virología , Adulto , Cohorte de Nacimiento , Antígenos de Grupos Sanguíneos/efectos adversos , Infecciones por Caliciviridae/diagnóstico , Femenino , Gastroenteritis/epidemiología , Genotipo , Humanos , Incidencia , Lactante , Masculino , Nicaragua/epidemiología , Norovirus/genética , Virus Norwalk , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto JovenRESUMEN
Noroviruses (NoV) are a leading cause of epidemic gastroenteritis. Human challenge studies have been used to examine the infectivity, pathogenicity, and host immune response to NoV as well as vaccine efficacy. The goal of this study was to conduct a meta-analysis of data from five previously completed human challenge trials and compare the response to the secondary NV inoculum (8fIIb) to its precursor (8fIIa). We investigated a total of 158 subjects: 76 subjects were experimentally challenged with NV inoculum 8fIIa, and 82 subjects were challenged with 8fIIb. We compared demographic characteristics, infection, illness, mean severity score, blood types, and duration of viral shedding between the two groups of subjects. There were no statistically significant differences in overall infection and illness rates between subjects inoculated with 8fIIa and 8fIIb. However, individuals challenged with 8fIIa had significantly higher severity scores (5.05 vs. 3.22, p = .008) compared with those challenged with 8fIIb. We also observed that infection with 8fIIb was associated with significantly longer duration of viral shedding compared with 8fIIa (11.0 days vs. 5.0 days, p = .0005). These results have serious implications for the development of new NoV inocula for human challenge studies to test candidate vaccine efficacy-where illness severity and duration of viral shedding are important outcomes.
Asunto(s)
Infecciones por Caliciviridae/virología , Virus Norwalk/clasificación , Virus Norwalk/patogenicidad , Esparcimiento de Virus , Adolescente , Adulto , Infecciones por Caliciviridae/inmunología , Relación Dosis-Respuesta Inmunológica , Femenino , Gastroenteritis/virología , Voluntarios Sanos , Experimentación Humana/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Virus Norwalk/genética , Virus Norwalk/inmunología , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Aim: We evaluated the efficacy of three ethanol-based hand rubs against murine norovirus in a proposed clinical simulation test (prEN 17430). Materials & methods: Virucidal activity was determined in 18 volunteers using three hand rubs: ethanol 72.4 and 89.5% v/v solutions, and 86% v/v gel. Subjects underwent testing with each product (3/6 ml for 15/30 s) and a reference solution (6 ml 70% v/v ethanol for 60 s). Results: Against murine norovirus, the reduction factors (RF; RF mean ± standard deviation log10 reduction of postsampling) for ethanol gel 86% v/v (RF 1.96 ± 0.64), ethanol 89.5% v/v (RF 2.49 ± 0.59) and ethanol 72.4% v/v (RF 2.61 ± 0.50), were all significantly superior to that of the reference solution. Conclusion: All three hand rubs passed the criteria set out in prEN 17430 and exhibited excellent virucidal efficacy.
Asunto(s)
Antiinfecciosos Locales/farmacología , Etanol/farmacología , Higiene de las Manos/métodos , Desinfectantes para las Manos/farmacología , Virus Norwalk/efectos de los fármacos , Antiinfecciosos Locales/química , Estudios Cruzados , Etanol/análisis , Mano/virología , Higiene de las Manos/normas , Desinfectantes para las Manos/química , Humanos , Factores de Tiempo , Carga Viral/efectos de los fármacosRESUMEN
BACKGROUND: Human noroviruses (HuNoV) are the leading cause of gastroenteritis. No vaccine is currently available to prevent norovirus illness or infection. Safe, infectious challenge strains are needed to assess vaccine efficacy in the controlled human infection model (CHIM). METHODS: A stock of HuNoV strain Norwalk virus ([NV] GI.1) was prepared. Healthy, genetically susceptible adults were inoculated with NV Lot 001-09NV and monitored for infection, gastroenteritis symptoms, and immune responses. RESULTS: Lot 001-09NV induced gastroenteritis in 9 (56%) and infection in 11 (69%) of 16 genetically susceptible subjects. All infected subjects developed strong immune responses to GI.1 with a 30-fold (geometric mean titer) increase in blocking titers (BT50) and a 161-fold increase in GI.1-specific immunoglobulin (Ig)G titers when compared with baseline. GI.1-specific cellular responses in peripheral blood were observed 9 days postchallenge with an average of 3253 IgA and 1227 IgG antibody-secreting cells per million peripheral blood mononuclear cells. CONCLUSIONS: GI.1 Lot 001-09NV appears to be similar in virulence to previous passages of NV strain 8fIIa. The safety profile, attack rate, and duration of illness make GI.1 Lot 001-09NV a useful challenge strain for future vaccine studies aimed at establishing immune correlates.
Asunto(s)
Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/virología , Gastroenteritis/prevención & control , Gastroenteritis/virología , Virus Norwalk/clasificación , Vacunas Virales/inmunología , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Norovirus is known as a major cause of several acute gastroenteritis (AGE) outbreaks each year. A study was conducted to develop a unique multi epitope subunit vaccine against human norovirus by adopting reverse vaccinology approach. The entire viral proteome of Norwalk virus was retrieved and allowed for further in silico study to predict highly antigenic epitopes through antigenicity, transmembrane topology screening, allergenicity assessment, toxicity analysis, population coverage analysis and molecular docking approach. Capsid protein VP1 and protein VP2 were identified as most antigenic viral proteins which generated a plethora of antigenic epitopes. Physicochemical properties and secondary structure of the designed vaccine were assessed to ensure its thermostability, hydrophilicity, theoretical PI and structural behavior. Molecular docking analysis of the refined vaccine with different MHCs and human immune TLR8 receptor demonstrated higher binding interaction as well. Complexed structure of the modeled vaccine and TLR8 showed minimal deformability at molecular level. The designed construct was reverse transcribed and adapted for E. coli strain K12 prior to insertion within pET28a(+) vector for its heterologous cloning and expression, and sequence of vaccine constructs showed no similarity with human proteins. However, the study could initiate in vitro and in vivo studies regarding effective vaccine development against human norovirus.
Asunto(s)
Proteínas de la Cápside/química , Biología Computacional/métodos , Virus Norwalk/inmunología , Vacunas de Subunidad/genética , Proteínas de la Cápside/inmunología , Simulación por Computador , Epítopos de Linfocito B/genética , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito T/genética , Epítopos de Linfocito T/inmunología , Antígenos HLA/metabolismo , Humanos , Simulación del Acoplamiento Molecular , Receptor Toll-Like 8/metabolismo , Vacunas de Subunidad/inmunologíaRESUMEN
Human noroviruses are the causative agents of non-bacterial gastroenteritis worldwide. The rapid onset and resolution of disease symptoms suggest that innate immune responses are critical for controlling norovirus infection; however, no effective antivirals are yet available. The present study was conducted to examine the antiviral activities of Schizonepeta tenuifolia Briquet extract (STE) against noroviruses. Treatment of human norovirus replicon-bearing HG23 cells with STE at 5 and 10 mg/ml concentrations resulted in the reduction in the viral RNA levels by 77.2% and 85.9%, respectively. STE had no cytotoxic effects on HG23 cells. Treatment of RAW 264.7 cells infected with murine norovirus 1 (MNV-1), a surrogate virus of human noroviruses, with STE at 10 and 20 µg/ml concentrations resulted in the reduction of viral replication by 58.5% and 84.9%, respectively. STE treatment induced the expression of mRNAs for type I and type II interferons in HG23 cells and upregulated the transcription of interferon-ß in infected RAW 264.7 cells via increased phosphorylation of interferon regulatory factor 3, a critical transcription regulator for type I interferon production. These results suggest that STE inhibits norovirus replication through the induction of antiviral interferon production during virus replication and may serve as a candidate antiviral substance for treatment against noroviruses.
Asunto(s)
Antivirales/farmacología , Infecciones por Caliciviridae/tratamiento farmacológico , Interferones/metabolismo , Lamiaceae/química , Norovirus/efectos de los fármacos , Extractos Vegetales/farmacología , Animales , Infecciones por Caliciviridae/virología , Línea Celular/efectos de los fármacos , Monoterpenos Ciclohexánicos , Humanos , Inmunidad Innata , Factor 3 Regulador del Interferón/metabolismo , Interferón Tipo I/metabolismo , Interferón gamma/metabolismo , Mentol/farmacología , Ratones , Monoterpenos/farmacología , Norovirus/patogenicidad , Virus Norwalk , Fitoquímicos/química , Fitoquímicos/farmacología , Sesquiterpenos Policíclicos , Células RAW 264.7 , ARN Viral , Sesquiterpenos/farmacología , Replicación Viral/efectos de los fármacosRESUMEN
Human norovirus (HuNoV) is a major cause of nonbacterial gastroenteritis worldwide, yet despite its impact on society, vaccines and antivirals are currently lacking. A HuNoV replicon system has been widely applied to the evaluation of antiviral compounds and has thus accelerated the process of drug discovery against HuNoV infection. Rupintrivir, an irreversible inhibitor of the human rhinovirus 3C protease, has been reported to inhibit the replication of the Norwalk virus replicon via the inhibition of the norovirus protease. Here we report, for the first time, the generation of rupintrivir-resistant human Norwalk virus replicon cells in vitro Sequence analysis revealed that these replicon cells contained amino acid substitutions of alanine 105 to valine (A105V) and isoleucine 109 to valine (I109V) in the viral protease NS6. The application of a cell-based fluorescence resonance energy transfer (FRET) assay for protease activity demonstrated that these substitutions were involved in the enhanced resistance to rupintrivir. Furthermore, we validated the effect of these mutations using reverse genetics in murine norovirus (MNV), demonstrating that a recombinant MNV strain with a single I109V substitution in the protease also showed reduced susceptibility to rupintrivir. In summary, using a combination of different approaches, we have demonstrated that, under the correct conditions, mutations in the norovirus protease that lead to the generation of resistant mutants can rapidly occur.
Asunto(s)
Antivirales/farmacología , Isoxazoles/farmacología , Virus Norwalk/efectos de los fármacos , Pirrolidinonas/farmacología , Proteasas Virales 3C , Secuencia de Aminoácidos , Línea Celular Tumoral , Cisteína Endopeptidasas/genética , Cisteína Endopeptidasas/metabolismo , Transferencia Resonante de Energía de Fluorescencia , Humanos , Mutación , Virus Norwalk/genética , Fenilalanina/análogos & derivados , Valina/análogos & derivados , Proteínas Virales/genética , Proteínas Virales/metabolismo , Replicación Viral/efectos de los fármacos , Replicación Viral/genéticaRESUMEN
The occurrence of hospital-acquired acute gastroenteritis (AGE) is a major concern for public health. RotavirusA (RVA) and norovirus (NoV) are common causes of viral AGE in the pediatric population, and their role in nosocomial infections has been proven, remaining poorly investigated. To investigate RVA and NoV in hospital-acquired AGE, 55 stool samples from children with nosocomial AGE were collected between May 2014 and May 2015. To evaluate virus spreading routes, 51 environmental swabs were collected from staff and patients' rooms. Stools were tested for both RVA and NoV RNA by reverse-transcription-PCR. Nucleotide sequencing and phylogenetic analysis were performed to characterize the viruses. Forty-seven of 55 cases analyzed resulted positive for RVA. The predominant genotype was G4P[8] (18/55) followed by G1P[8] (14/55). Mixed RVA infections were also detected (7/55). Twenty-two samples were positive for NoV, and GII.4 was revealed to be the predominant genotype. Seventeen samples were positive for both RVA and NoV. This study aimed to evaluate the burden of norovirus and rotavirus nosocomial AGE, contributing to identify the environment source of infections and to activate effective strategies for intervention. The reduction in nosocomial AGE cases is an important aspect, considered the worsened disease course in transplant, cancer, and intensive care unit inpatients.
Asunto(s)
Infecciones por Caliciviridae/epidemiología , Infección Hospitalaria/epidemiología , Gastroenteritis/epidemiología , Gastroenteritis/virología , Unidades Hospitalarias , Pediatría , Infecciones por Rotavirus/epidemiología , Enfermedad Aguda/epidemiología , Adolescente , Infecciones por Caliciviridae/virología , Niño , Preescolar , Infección Hospitalaria/virología , Heces/virología , Femenino , Genotipo , Humanos , Lactante , Italia/epidemiología , Masculino , Mamastrovirus/genética , Mamastrovirus/aislamiento & purificación , Norovirus/genética , Norovirus/aislamiento & purificación , Virus Norwalk/genética , Virus Norwalk/aislamiento & purificación , Filogenia , Estudios Prospectivos , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Rotavirus/genética , Rotavirus/aislamiento & purificación , Infecciones por Rotavirus/virología , Análisis de Secuencia de ADNRESUMEN
An outbreak of gastroenteritis affected 453 attendees (attack rate 28·5%) of six separate events held at a hotel in Singapore. Active case detection, case-control studies, hygiene inspections and microbial analysis of food, environmental and stool samples were conducted to determine the aetiology of the outbreak and the modes of transmission. The only commonality was the food, crockery and cutlery provided and/or handled by the hotel's Chinese banquet kitchen. Stool specimens from 34 cases and 15 food handlers were positive for norovirus genogroup II. The putative index case was one of eight norovirus-positive food handlers who had worked while they were symptomatic. Several food samples and remnants tested positive for Escherichia coli or high faecal coliforms, aerobic plate counts and/or total coliforms, indicating poor food hygiene. This large common-source outbreak of norovirus gastroenteritis was caused by the consumption of contaminated food and/or contact with contaminated crockery or cutlery provided or handled by the hotel's Chinese banquet kitchen.
Asunto(s)
Infecciones por Caliciviridae/epidemiología , Brotes de Enfermedades , Gastroenteritis/epidemiología , Gastroenteritis/virología , Norovirus/aislamiento & purificación , Adolescente , Adulto , Aerobiosis , Anciano , Estudios de Casos y Controles , Niño , Preescolar , Microbiología Ambiental , Escherichia coli , Heces/virología , Femenino , Contaminación de Alimentos , Humanos , Lactante , Masculino , Persona de Mediana Edad , Norovirus/clasificación , Norovirus/genética , Virus Norwalk , Singapur/epidemiología , Adulto JovenRESUMEN
The need for improved pathogen separation and concentration methods to reduce time-to-detection for foodborne pathogens is well recognized. Apolipoprotein H (ApoH) is an acute phase human plasma protein that has been previously shown to interact with viruses, lipopolysaccharides (LPS) and bacterial proteins. The purpose of this study was to determine if ApoH was capable of binding and efficiently capturing two representative human norovirus strains (GI.1 and GII.4), a cultivable surrogate, and four bacterial pathogens (Escherichia coli O157:H7, Listeria monocytogenes, Salmonella enterica serovar Enteritidis, and Staphylococcus aureus). Experiments were carried out using an ApoH-conjugated magnetic bead-based capture followed by pathogen detection using nucleic acid amplification. For all three viruses studied, >10% capture efficiency (<1 Log10 loss in RT-qPCR amplifiable units) was observed. The same capture efficiencies were observed for the bacterial pathogens tested, with the exception of E. coli O157:H7 (approximately 1% capture efficiency, or 2 Log10 loss in CFU equivalents). The efficiency of the capture steps did not vary as a consequence of input target concentration or in the presence of an abundance of background microflora. A complementary plate-based capture assay showed that ApoH bound to a variety of human norovirus virus-like particles. ApoH has the potential to be a broadly reactive ligand for separating and concentrating representative foodborne pathogens, both bacteria and viruses.
Asunto(s)
ADN Bacteriano/aislamiento & purificación , Contaminación de Alimentos/análisis , Enfermedades Transmitidas por los Alimentos/diagnóstico , ARN Viral/aislamiento & purificación , beta 2 Glicoproteína I/química , Recuento de Colonia Microbiana , Escherichia coli O157/aislamiento & purificación , Microbiología de Alimentos , Enfermedades Transmitidas por los Alimentos/microbiología , Enfermedades Transmitidas por los Alimentos/virología , Listeria monocytogenes/aislamiento & purificación , Virus Norwalk/aislamiento & purificación , Reacción en Cadena en Tiempo Real de la Polimerasa , Salmonella enteritidis/aislamiento & purificación , Análisis de Secuencia de ARN , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
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 isolation and characterization of human monoclonal IgG and IgA antibodies against a GI.I NoV, Norwalk virus (NV). A higher proportion of the IgA antibodies blocked NV VLP binding to glycans than did IgG antibodies. We generated isotype-switched variants of IgG and IgA antibodies to study the effects of the constant domain on blocking and binding activities. The IgA form of antibodies appears to be more potent than the IgG form in blocking norovirus binding to histo-blood group antigens. These studies suggest a unique role for IgA antibodies in protection from NoV infections by blocking attachment to cell receptors.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Linfocitos B/inmunología , Antígenos de Grupos Sanguíneos/inmunología , Infecciones por Caliciviridae/inmunología , Western Blotting , Línea Celular , Ensayo de Inmunoadsorción Enzimática , Gastroenteritis/inmunología , Humanos , Hibridomas , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Virus Norwalk/inmunología , Reacción en Cadena de la PolimerasaRESUMEN
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 to amino acids 21-32 (LVPEVNASDPLA) of the NV S domain, and its specificity was verified by epitope transfer and reactivity with a recombinant MAb NV10 single-chain variable fragment (scFv). Comparative structural modeling of the NV10 strain-specific and the broadly cross-reactive TV20 epitopes identified two internal non-overlapping sites in the NV shell, corresponding to variable and conserved amino acid sequences among strains, respectively. The S domain, like the P domain, contains strain-specific epitopes that contribute to the antigenic diversity among the noroviruses.
Asunto(s)
Anticuerpos Antivirales/química , Proteínas de la Cápside/química , Epítopos/química , Virus Norwalk/inmunología , Anticuerpos de Cadena Única/química , Secuencia de Aminoácidos , Animales , Anticuerpos Monoclonales/biosíntesis , Anticuerpos Monoclonales/química , Anticuerpos Antivirales/biosíntesis , Calicivirus Felino/genética , Calicivirus Felino/metabolismo , Cápside/química , Cápside/inmunología , Proteínas de la Cápside/genética , Proteínas de la Cápside/inmunología , Mapeo Epitopo , Epítopos/genética , Epítopos/inmunología , Expresión Génica , Ratones , Ratones Endogámicos BALB C , Modelos Moleculares , Datos de Secuencia Molecular , Virus Norwalk/genética , Estructura Terciaria de Proteína , Alineación de Secuencia , Anticuerpos de Cadena Única/biosíntesisRESUMEN
The aim of the study was to investigate mental health and resilience in adolescents who have been internationally adopted and their non-adopted peers and examine the potential interaction between adoption status and resilience on mental health problems. Data from the population based youth@hordaland-survey, conducted in Hordaland County, Norway, in 2012 was used. In all, 10 257 adolescents aged 16-19 years provided self-reported data on several mental health instruments. Of these, 45 adolescents were identified as internationally adopted. Adoptees reported more symptoms of depression, attention-deficit/hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD) and perfectionism than non-adopted adolescents, but there were no differences regarding resilience. Adolescents with higher resilience scores reported fewer symptoms of mental health problems, however, no interaction effects were found for adoption status and total resilience score on measures of mental health problems. Our findings indicate that knowledge of resilience factors can form the basis for preventive interventions.
Asunto(s)
Adopción/psicología , Trastornos Mentales/epidemiología , Resiliencia Psicológica , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/etiología , Trastorno por Déficit de Atención con Hiperactividad/psicología , Depresión/epidemiología , Depresión/etiología , Depresión/psicología , Femenino , Humanos , Masculino , Trastornos Mentales/etiología , Trastornos Mentales/psicología , Virus Norwalk , Trastorno Obsesivo Compulsivo/epidemiología , Trastorno Obsesivo Compulsivo/etiología , Trastorno Obsesivo Compulsivo/psicología , Escalas de Valoración Psiquiátrica , Pruebas Psicológicas , Adulto JovenRESUMEN
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. Furthermore, the Norwalk virus-specific IgG response induced in mice by Newcastle disease virus vectors was similar to that induced by baculovirus-expressed virus-like particles in mice. However, the modified rBC vector in the presence of VP2 protein induced significantly higher levels of cellular and mucosal immune responses than those induced by baculovirus-expressed VLPs. These results indicate that Newcastle disease virus has great potential for developing a live Norwalk virus vaccine by inducing humoral, cellular and mucosal immune responses in humans.
Asunto(s)
Proteínas de la Cápside/inmunología , Virus de la Enfermedad de Newcastle/genética , Virus Norwalk/inmunología , Vacunas de Partículas Similares a Virus/inmunología , Vacunas Virales/inmunología , Animales , Anticuerpos Antivirales/sangre , Proteínas de la Cápside/genética , Femenino , Vectores Genéticos , Inmunidad Celular , Inmunidad Mucosa , Inmunoglobulina G/sangre , Ratones Endogámicos BALB C , Virus Norwalk/genética , Resultado del Tratamiento , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/genética , Vacunas de Subunidad/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología , Vacunas de Partículas Similares a Virus/administración & dosificación , Vacunas de Partículas Similares a Virus/genética , Vacunas Virales/administración & dosificación , Vacunas Virales/genéticaRESUMEN
To explore the etiological spectrum of diarrhea and its epidemiological characteristics in diarrhea symptoms surveillance cases younger than 5 years from 2009 to 2013 in Gansu province, northwest China. Systematic diarrhea symptoms surveillance were conducted in 27 sentinel sites in Gansu province and outpatients with three or more loose, watery, or sticky pus stools per day were defined as surveillance cases. All stool specimens were tested for Rotavirus, Human calicivirus, Adenovirus, and Astrovirus. Totally, 1,119 cases (51.54%) were identified as any enteric virus. The average isolation rate of Rotavirus was 51.13%, Astrovirus was 10.84%, Adenovirus was 6.94%, and Human calicivirus was 6.60% (P < 0.01). Rotavirus was identified with the highest frequency among these enteric pathogens except in 2011, with a notable downward trend over time (P < 0.01). Rotavirus A was the most proportion in rotavirus, G3P[8] and G9P[8] were the most common combination. Rotavirus mixed Human calicivirus infections was the most common mixed infected patterns. Viral-positive rate was higher among children aged group of 0-12 and 13-24 months (P < 0.01, respectively). The isolation rates of four enteric viral pathogens showed a similar distinct seasonal variation with a higher rate in spring, autumn, and winter months. Rotavirus was the major epidemiological viral pathogen in diarrhea symptom surveillance cases in Gansu province, northwest China, during period 2009-2013. Seasonal and age-related variations were observed in enteric viral pathogen isolation rate. The comprehensive and continuous surveillance is needed to identify the prevalence of different enteric viral pathogens.
Asunto(s)
Adenoviridae/aislamiento & purificación , Diarrea/epidemiología , Mamastrovirus/aislamiento & purificación , Norovirus/aislamiento & purificación , Rotavirus/aislamiento & purificación , Vigilancia de Guardia , Virosis/epidemiología , Preescolar , China/epidemiología , Coinfección/epidemiología , Coinfección/virología , Diarrea/virología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Virus Norwalk , Prevalencia , Virosis/virologíaRESUMEN
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 asymptomatic individuals. Saliva was collected at the challenge, and two weeks and 40 days post-challenge. Samples were analyzed using the Luminex fluorometric and Meso Scale Discovery (MSD) electrochemiluminescence immunoassays. Recombinant P domains of Norwalk virus capsid protein, as well as similar recombinant proteins of two genogroup II noroviruses (VA387 and VA207) were used as antigens. Immunoconversions were defined as >4-fold increase in antibody responses to the norovirus antigens. Various sample pre-treatment options, buffers, saliva dilution ratios, and data adjustment approaches to control for sample-to-sample variability in saliva composition were compared using the Luminex assay. The results suggest that adjusting responses to the norovirus antigens for responses to the protein purification tag, glutathione-S-transferase (GST), significantly improved the odds of producing a correct immunoconversion test result. IgG-based tests were more accurate compared to IgA-based tests. At optimal conditions, both Luminex and MSD assays for Norwalk-specific IgG antibodies correctly identified all infected and non-infected individuals. There was no evidence of cross-reactivity of anti-Norwalk virus antibodies with genogroup II noroviruses. These results suggest that salivary antibody responses can be used for the detection of incident infections with Norwalk virus in prospective surveys.
Asunto(s)
Anticuerpos Antivirales/inmunología , Infecciones por Caliciviridae/diagnóstico , Infecciones por Caliciviridae/inmunología , Fluoroinmunoensayo/métodos , Gastroenteritis/diagnóstico , Gastroenteritis/inmunología , Virus Norwalk/inmunología , Saliva/inmunología , Voluntarios Sanos , Humanos , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
O presente artigo tem por objetivo avaliar associação entre fatores de risco cardiovascular (FRCV) e indicadores antropométricos em amostra de base populacional de universitários de São Luís/MA. Estudo transversal com 968 universitários, mediana de 22 anos. Glicemia, triglicerídeos (TGL), HDL-c, tabagismo, consumo de álcool, sedentarismo, síndrome metabólica (SM–critérios do Joint Interim Statement) e resistência insulínica (RI), foram associados e correlacionados com os indicadores antropométricos Índice de Massa Corporal (IMC), Circunferência da Cintura (CC), Relação Cintura Quadril (RCQ) e Relação Cintura Altura (RCA). Encontraram-se associações entre TGL, HAS, SM e maiores valores de todas as variáveis antropométricas. RI associou-se a maiores valores IMC e RCA em homens e mulheres. Baixo HDL-c foi associado a maiores valores de todas as variáveis antropométricas em mulheres. Consumo de álcool associou-se a valores mais elevados de IMC e CC em mulheres e RCQ e RCA em homens. Fumo associou-se a maiores valores de RCA em ambos os sexos. Sedentarismo foi associado a maiores valores de RCQ apenas em homens. As correlações mais altas foram estabelecidas para mulheres entre TGL e IMC, CC, RCQ e RCA. Os indicadores que mais se associaram aos FRCV foram IMC, CC e RCA em mulheres e RCQ e RCA em homens.
The article aims to evaluate the relation between cardiovascular risk factors (CVRF) and anthropometric indicators in a sample of university students from São Luís-MA, Brazil. It is a cross-sectional study conducted with 968 university students, with median age of 22. Glycemia, triglycerides, HDL-c, smoking, alcohol consumption, physical inactivity, metabolic syndrome (Joint Interim Statement criteria) and insulin resistance (IR), were associated and correlated with anthropometric indicators such as BMI, WC, WHR and WHtR. Associations were found between TGL, SH, SM and higher values of all anthropometric variables. The RI was associated with higher BMI values and WHtR in men and women. The low HDL-c was associated with higher values of all anthropometric variables in women. Consumption of alcohol was associated with higher values of BMI and WC in women and WHR in men and WHtR. Smoking was associated with higher values of WHtR in both sexes. Physical inactivity was associated with higher values of WHR in men only. The highest correlations were established for women between TGL and BMI CC, WHR and WHtR. The indicators most associated with CVRF were BMI, WC and WHtR in females and WHR and WHtR in men.
Asunto(s)
Proteasas de Cisteína/metabolismo , Inhibidores de Cisteína Proteinasa/síntesis química , Inhibidores de Cisteína Proteinasa/farmacología , Diseño de Fármacos , Virus Norwalk/enzimología , Técnicas de Química Sintética , Cristalografía por Rayos X , Inhibidores de Cisteína Proteinasa/química , Relación Dosis-Respuesta a Droga , Modelos Moleculares , Conformación Molecular , Estereoisomerismo , Relación Estructura-ActividadRESUMEN
BACKGROUND: Noroviruses are a leading cause of acute gastroenteritis worldwide. Mucosal and cellular immune responses remain poorly understood, with most studies of noroviruses having focused on serological responses to infection. METHODS: We used saliva, feces, and peripheral blood mononuclear cells collected from persons who were administered Norwalk virus (NV) to characterize mucosal (salivary and fecal immunoglobulin A [IgA]) and cellular (NV-specific IgA and immunoglobulin G [IgG] antibody-secreting cells and total and NV-specific IgA and IgG memory B cells) immune responses following infection. RESULTS: Prechallenge levels of NV-specific salivary IgA and NV-specific memory IgG cells correlated with protection from gastroenteritis, whereas prechallenge levels of NV-specific fecal IgA correlated with a reduced viral load. Antibody-secreting cell responses were biased toward IgA, while memory B-cell responses were biased toward IgG. NV-specific memory B cells but not antibody-secreting cells persisted 180 days after infection. CONCLUSIONS: NV-specific salivary IgA and NV-specific memory IgG cells were identified as new correlates of protection against NV gastroenteritis. Understanding the relative importance of mucosal, cellular, and humoral immunity is important in developing vaccine strategies for norovirus disease prevention.
Asunto(s)
Anticuerpos Antivirales/inmunología , Infecciones por Caliciviridae/inmunología , Gastroenteritis/inmunología , Inmunoglobulina A/inmunología , Inmunoglobulina G/inmunología , Virus Norwalk/inmunología , Adulto , Anticuerpos Antivirales/sangre , Infecciones por Caliciviridae/virología , Heces/química , Gastroenteritis/virología , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Leucocitos Mononucleares/inmunología , Saliva/químicaRESUMEN
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 antibody response in the context of an experimental challenge study with a human NoV. Heterotypic histo-blood group antigen (HBGA)-blocking activity against GI.4, GI.7, and GII.4 NoVs increased significantly in the serum of individuals (n = 18) infected with Norwalk virus (GI.1). Although the fold increases and peak titers of heterotypic antibody were more modest than titers of antibody reactive with the challenge antigen, Norwalk virus infection elicited a serological rise even against the novel Sydney variant of GII.4 NoVs. These observations indicate that the development of a broadly cross-protective NoV vaccine containing a limited number of genotypes may be possible.