RESUMEN

PURPOSE OF REVIEW: Viruses are the most common etiological agents of diarrhea in children. Despite rotavirus vaccine introduction, rotavirus remains as the leading cause of death globally, followed by norovirus, which represents a diagnostic challenge. Here, we describe new advances in the diagnosis and management of viral diarrheas. RECENT FINDINGS: Although immunoassays are widely used for their fast turnaround time and low cost, molecular techniques have become the most reliable diagnostic method due to their high sensitivity and capacity to analyze multiple pathogens in gastrointestinal panels. Isothermal nucleic acid amplification assays (LAMP and RPA) are promising techniques since they do not require sophisticated equipment and can be used as point-of-care testing. CRISPR/Cas nucleic acid detection systems are new diagnostic methods with great potential. Several recent published articles describe the role of human intestinal enteroids to characterize norovirus infection, to test new drugs, and for vaccine development. The interaction between the human gut microbiota and gastrointestinal viral infections has been extensively reviewed and offers some innovative mechanisms for therapeutic and preventive measures. SUMMARY: Although important advances have been made, more research is needed to address remaining challenges and further improve diagnostic capabilities and better management strategies for this critical infectious disease.

Asunto(s)

Diarrea , Humanos , Diarrea/diagnóstico , Diarrea/virología , Diarrea/terapia , Técnicas de Diagnóstico Molecular/métodos , Virosis/diagnóstico , Virosis/terapia , Norovirus/genética , Norovirus/aislamiento & purificación , Infecciones por Caliciviridae/diagnóstico , Infecciones por Caliciviridae/terapia , Técnicas de Amplificación de Ácido Nucleico/métodos , Microbioma Gastrointestinal

RESUMEN

BACKGROUND: Rabbit hemorrhagic disease (RHD) is an acute infectious disease that damages the rabbit industry by producing significant mortality rates in young and adult rabbits. RHD is better controlled by vaccination. OBJECTIVE: The current study's goal was to prepare and evaluate the immuno-enhancing effect of montanide ISA70 and aluminum hydroxide (Al(OH)3) gel incorporated within the inactivated RHDV2 vaccine and assess the vaccine's protective efficacy against the homologous and heterologous local RHDV2 strains in rabbits. METHODS: Inactivated RHDV vaccines were prepared using Montanide ISA70 oil or Al(OH)3 gel adjuvants and submitted to sterility, safety, and potency tests. 200 rabbits were equally divided into 4 groups: G1 (control), G2 (vaccinated with gel-incorporated vaccine), G3 (vaccinated with montanide-incorporated vaccine), and G4 (vaccinated with gel- and montanide-incorporated vaccines). Individual blood samples were collected from one week to six months from all groups. The vaccine's potency was measured by the HI test and protection percentage post challenge. RESULTS: Data revealed slightly increasing HI titer means reaching the 1st peak at 4 weeks post-vaccination (7.33, 7.67, and 7.33 log2 in the 2nd, 3rd, and 4th groups, respectively), then slightly decreasing and peaked again, giving 9.33 log2 for the2nd group at 3 months post-vaccination (MPV), 10.67 log2 for 3rd the group, and 10.33 log2 for the 4th group at 5 months post-vaccination. Titer gradually decreased but remained protective. The protection rate ranged from 80-100% and 80-90% for homologous and heterologous local RHDV2 vaccines, respectively, within 3 weeks and 6 months post-challenge. The montanide oil RHDV2 vaccine induced better protection than the aluminum gel RHDV2 vaccine. CONCLUSION: The results demonstrated evidence of cross-protection between RHDV2 strains. The oil emulsion vaccine induced higher and longer-lasting antibody titers than those obtained with the RHDV2 aluminum gel vaccine.

Asunto(s)

Hidróxido de Aluminio , Infecciones por Caliciviridae , Virus de la Enfermedad Hemorrágica del Conejo , Vacunas Virales , Animales , Conejos , Hidróxido de Aluminio/farmacología , Hidróxido de Aluminio/administración & dosificación , Virus de la Enfermedad Hemorrágica del Conejo/inmunología , Vacunas Virales/inmunología , Infecciones por Caliciviridae/veterinaria , Infecciones por Caliciviridae/prevención & control , Geles , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/administración & dosificación , Vacunas de Productos Inactivados/inmunología , Ácidos Oléicos/farmacología , Ácidos Oléicos/administración & dosificación

RESUMEN

MicroRNAs (miR) are a group of small, non-coding RNAs of 17-25 nucleotides that regulate gene expression at the post-transcriptional level. Dysregulation of miRNA expression or function may contribute to abnormal gene expression and signaling pathways, leading to disease pathology. Lagovirus europaeus (L. europaeus) causes severe disease in rabbits called rabbit hemorrhagic disease (RHD). The symptoms of liver, lung, kidney, and spleen degeneration observed during RHD are similar to those of acute liver failure (ALF) and multi-organ failure (MOF) in humans. In this study, we assessed the expression of miRs and their target genes involved in the innate immune and inflammatory response. Also, we assessed their potential impact on pathways in L. europaeus infection-two genotypes (GI.1 and GI.2)-in the liver, lungs, kidneys, and spleen. The expression of miRs and target genes was determined using quantitative real-time PCR (qPCR). We assessed the expression of miR-155 (MyD88, TAB2, p65, NLRP3), miR-146a (IRAK1, TRAF6), miR-223 (TLR4, IKKα, NLRP3), and miR-125b (MyD88). We also examined biomarkers of inflammation: IL-1ß, IL-6, TNF-α, and IL-18 in four tissues at the mRNA level. Our study shows that the main regulators of the innate immune and inflammatory response in L. europaeus/GI.1 and GI.2 infection, as well as RHD, are miR-155, miR-223, and miR-146a. During infection with L. europaeus/RHD, miR-155 has both pro- and anti-inflammatory effects in the liver and anti-inflammatory effects in the kidneys and spleen; miR-146a has anti-inflammatory effects in the liver, lungs and kidneys; miR-223 has anti-inflammatory effects in all tissues; however, miR-125b has anti-inflammatory effects only in the liver. In each case, such an effect may be a determinant of the pathogenesis of RHD. Our research shows that miRs may regulate three innate immune and inflammatory response pathways in L. europaeus infection. However, the result of this regulation may be influenced by the tissue microenvironment. Our research shows that infection of rabbits with L. europaeus/GI.1 and GI.2 genotypes causes an overexpression of two critical acute phase cytokines: IL-6 in all examined tissues and TNF-α (in the liver, lungs, and spleen). IL-1ß was highly expressed only in the lungs after L. europaeus infection. These facts indicate a strong and rapid involvement of the local innate immune and inflammatory response in L. europaeus infection-two genotypes (GI.1 and GI.2)-and in the pathogenesis of RHD. Profile of biomarkers of inflammation in rabbits infected with L. europaeus/GI.1 and GI.2 genotypes are similar regarding the nature of changes but are different for individual tissues. Therefore, we propose three inflammation profiles for L. europaeus infection for both GI.1 and GI.2 genotypes (pulmonary, renal, liver, and spleen).

Asunto(s)

Infecciones por Caliciviridae , Genotipo , Virus de la Enfermedad Hemorrágica del Conejo , Inmunidad Innata , MicroARNs , Animales , MicroARNs/genética , Inmunidad Innata/genética , Conejos , Infecciones por Caliciviridae/genética , Infecciones por Caliciviridae/inmunología , Infecciones por Caliciviridae/virología , Virus de la Enfermedad Hemorrágica del Conejo/genética , Virus de la Enfermedad Hemorrágica del Conejo/inmunología , Inflamación/genética , Inflamación/inmunología , Regulación de la Expresión Génica , Hígado/metabolismo , Hígado/patología , Hígado/virología

RESUMEN

Norovirus infection is characterised by a rapid onset of disease and the development of debilitating symptoms including projectile vomiting and diffuse diarrhoea. Vaccines and antivirals are sorely lacking and developments in these areas are hampered by the lack of an adequate cell culture system to investigate human norovirus replication and pathogenesis. Herein, we describe how the model norovirus, Mouse norovirus (MNV), produces a viral protein, NS3, with the functional capacity to attenuate host protein translation which invokes the activation of cell death via apoptosis. We show that this function of NS3 is conserved between human and mouse viruses and map the protein domain attributable to this function. Our study highlights a critical viral protein that mediates crucial activities during replication, potentially identifying NS3 as a worthy target for antiviral drug development.

Asunto(s)

Infecciones por Caliciviridae , Macrófagos , Norovirus , Norovirus/fisiología , Animales , Ratones , Infecciones por Caliciviridae/virología , Macrófagos/virología , Macrófagos/metabolismo , Humanos , Biosíntesis de Proteínas , Replicación Viral/fisiología , Muerte Celular/fisiología , Proteínas no Estructurales Virales/metabolismo , Proteínas no Estructurales Virales/genética , Apoptosis

RESUMEN

Human noroviruses (HuNoVs) are a leading cause of acute viral gastroenteritis worldwide. Infectious outbreaks due to recombinant NoV genotype called GII.P16-GII.2 have been frequently reported since 2016. In this study, we expressed the major capsid protein VP1 from three GII.2 NoV strains using the recombinant baculovirus expression system. The assembly, histo-blood group antigen (HBGA)-binding patterns, and cross-blocking abilities of VP1 proteins were investigated. All the three NoV VP1 proteins successfully assembled into virus-like particles (VLPs). The HBGA-binding assay demonstrated a temporal binding pattern. The latest isolate bound to saliva samples of all blood types. Sequence alignment suggested that the observed gain in HBGA-binding ability was attributed to a limited number of amino acid mutations. Using chimeric VP1 proteins, we demonstrated that synergistic effects resulted in enhanced binding ability. Bile salts increased GII.2 VLP avidity for HBGAs except GII.2-2011/M1. In vitro blockade assay of salivary HBGA-VLP binding demonstrated the presence of cross-blocking effects among different strains. This study provides insight into the evolutionary binding characteristics and cross-blocking effects of GII.2 NoVs to facilitate the development of measures to control this type of viruses.

Asunto(s)

Antígenos de Grupos Sanguíneos , Proteínas de la Cápside , Norovirus , Norovirus/genética , Norovirus/metabolismo , Proteínas de la Cápside/genética , Proteínas de la Cápside/metabolismo , Proteínas de la Cápside/inmunología , Humanos , Antígenos de Grupos Sanguíneos/metabolismo , Infecciones por Caliciviridae/virología , Infecciones por Caliciviridae/inmunología , Unión Proteica , Genotipo , Saliva/virología , Gastroenteritis/virología , Secuencia de Aminoácidos

RESUMEN

Breastfeeding provides infection protection for several pathogens but not for noroviruses. Mechanisms explaining this discrepancy have been unclear. In this issue of Cell Host & Microbe, Peiper et al. demonstrate that while breastmilk protects mice from intestinal damage, it promotes neonatal murine norovirus infection due to maternal-derived bile acids.1.

Asunto(s)

Ácidos y Sales Biliares , Infecciones por Caliciviridae , Leche Humana , Norovirus , Animales , Ácidos y Sales Biliares/metabolismo , Infecciones por Caliciviridae/virología , Ratones , Leche Humana/virología , Leche Humana/química , Humanos , Femenino , Lactancia Materna , Gastroenteritis/virología

RESUMEN

Sapovirus (SaV) infection is increasing worldwide. Herein, we provided evidence of a significant increase in SaV infection in Japan during 2010-2022, primarily due to the considerable (p = 0.0003) rise of the GI.1 genotype. Furthermore, we found that all major and minor SaV outbreaks in Japan, including the largest SaV outbreak in 2021-2022, were caused by the GI.1 genotype. Therefore, to get insight into the underlying molecular mechanism behind this rising trend of the SaV GI.1 type, we selected 15 SaV GI.1 outbreak strains for complete genome analysis through next-generation sequencing. Phylogenetically, our strains remained clustered in different branches in lineages I and II among the GI.1 genotype. We showed all amino acid (aa) substitutions in different open reading frames (ORFs) in these strains. Importantly, we have demonstrated that the strains involved in the largest SaV outbreak in Japan in 2021-2022 belonged to lineage II and possessed the third ORF. We have identified some unique aa mutations in these major outbreak strains in the NS1 and NS6-NS7 regions that are thought to be associated with viral pathogenicity, cell tropism, and epidemiological competence. Thus, in addition to enriching the database of SaV's complete sequences, this study provides insights into its important mutations.

Asunto(s)

Infecciones por Caliciviridae , Brotes de Enfermedades , Evolución Molecular , Genoma Viral , Genotipo , Sistemas de Lectura Abierta , Filogenia , Sapovirus , Sapovirus/genética , Sapovirus/clasificación , Sapovirus/aislamiento & purificación , Humanos , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología , Japón/epidemiología , Genoma Viral/genética , Sistemas de Lectura Abierta/genética , Gastroenteritis/virología , Gastroenteritis/epidemiología , Secuenciación de Nucleótidos de Alto Rendimiento , Sustitución de Aminoácidos , Epidemiología Molecular , Secuenciación Completa del Genoma , Mutación

RESUMEN

Mexico is home to 14 species of lagomorphs, 6 of which are endemic. Studies on diseases affecting native lagomorphs are scarce, and in most cases, the impact on their populations remains largely unknown. Rabbit hemorrhagic disease virus (RHDV), especially the RHDV2 variant, causes a serious and extremely contagious disease, resulting in high mortality rates and major declines in wild lagomorph populations. The objectives of this study were to identify disease hotspots and critical biodiversity regions in Mexico through the combined use of disease information and lagomorph distribution maps and to determine the areas of greatest concern. In total, 19 states of Mexico recorded RHDV2 from April 2020 to August 2021, and 12 of them reported the wild species Sylvilagus audubonii, Lepus californicus, and unidentified Leporidae species. The distribution of RHDV2 in Mexico can be closely predicted from climatic variables. RHDV2 hotspots are located in the central-southern area of the Mexican Highlands and the Trans-Mexican Volcanic Belt, where the virus affects multiple species. This knowledge is essential for proposing specific actions to manage and preserve lagomorph populations at risk and address these issues as soon as possible.

Asunto(s)

Infecciones por Caliciviridae , Virus de la Enfermedad Hemorrágica del Conejo , Lagomorpha , Animales , México/epidemiología , Virus de la Enfermedad Hemorrágica del Conejo/genética , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología , Infecciones por Caliciviridae/veterinaria , Lagomorpha/virología , Clima , Conejos , Animales Salvajes/virología , Biodiversidad

RESUMEN

Wastewater-based epidemiology (WBE) gained widespread use as a tool for supporting clinical disease surveillance during the COVID-19 pandemic. There is now significant interest in the continued development of WBE for other pathogens of clinical significance. In this study, approximately 3,200 samples of wastewater from across England, previously collected for quantification of SARS-CoV-2, were re-analysed for the quantification of norovirus genogroup I (GI) and II (GII). Overall, GI and GII were detected in 93% and 98% of samples respectively, and at least one of the genogroups was detected in 99% of samples. GI was found at significantly lower concentrations than GII, but the proportion of each genogroup varied over time, with GI becoming more prevalent than GII in some areas towards the end of the study period (May 2021 - March 2022). Using relative strength indices (RSI), it was possible to study the trends of each genogroup, and total norovirus over time. Increases in norovirus levels appeared to coincide with the removal of COVID-19 related lockdown restrictions within England. Local Moran's I analyses indicated several localised outbreaks of both GI and GII across England, notably the possible GI outbreak in the north of England in early 2022. Comparisons of national average norovirus concentrations in wastewater against concomitant norovirus reported case numbers showed a significant linear relationship. This highlights the potential for wastewater-based monitoring of norovirus as a valuable approach to support surveillance of norovirus in communities.

Asunto(s)

Norovirus , Aguas Residuales , Norovirus/aislamiento & purificación , Norovirus/genética , Aguas Residuales/virología , Inglaterra/epidemiología , Humanos , COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2 , Monitoreo Epidemiológico Basado en Aguas Residuales , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología

RESUMEN

Norovirus (NoV) is the main pathogen that causes acute gastroenteritis and brings a heavy socio-economic burden worldwide. In this study, five polysaccharide fractions, labeled pSFP-1-5, were isolated and purified from Sargassum fusiforme (S. fusiforme). In vitro experiments demonstrated that pSFP-5 significantly prevented the binding of type A, B and H histo-blood group antigens (HBGAs) to NoV GII.4 virus-like particles (NoV GII.4 VLPs). In addition, in vivo experiments revealed that pSFP-5 was effective in reducing the accumulation of NoV in oysters, indicating that pSFP-5 could reduce the risk of NoV infection from oyster consumption. The results of transmission electron microscopy showed that the appearance of NoV GII.4 VLPs changed after pSFP-5 treatment, indicating that pSFP-5 may achieve antiviral ability by altering the morphological structure of the viral particles so that they could not bind to HBGAs. The results of the present study indicate that pSFP-5 may be an effective anti-NoV substance and can be used as a potential anti-NoV drug component.

Asunto(s)

Antígenos de Grupos Sanguíneos , Infecciones por Caliciviridae , Norovirus , Polisacáridos , Sargassum , Norovirus/efectos de los fármacos , Sargassum/química , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/metabolismo , Animales , Antígenos de Grupos Sanguíneos/metabolismo , Infecciones por Caliciviridae/virología , Infecciones por Caliciviridae/tratamiento farmacológico , Humanos , Gastroenteritis/virología , Gastroenteritis/tratamiento farmacológico , Antivirales/farmacología , Antivirales/química , Ostreidae/virología , Virión/metabolismo , Virión/ultraestructura , Virión/efectos de los fármacos , Algas Comestibles

RESUMEN

The pathogenic outcome of enteric virus infections is governed by a complex interplay between the virus, intestinal microbiota, and host immune factors, with metabolites serving as a key mediator. Noroviruses bind bile acid metabolites, which are produced by the host and then modified by commensal bacteria. Paradoxically, bile acids can have both proviral and antiviral roles during norovirus infections. Working in an infant mouse model of norovirus infection, we demonstrate that microbiota and their bile acid metabolites protect from norovirus diarrhea, whereas host bile acids promote disease. We also find that maternal bile acid metabolism determines the susceptibility of newborn mice to norovirus diarrhea during breastfeeding. Finally, targeting maternal and neonatal bile acid metabolism can protect newborn mice from norovirus disease. In summary, neonatal metabolic immaturity and breastmilk bile acids are central determinants of heightened newborn vulnerability to norovirus disease.

Asunto(s)

Animales Recién Nacidos , Ácidos y Sales Biliares , Infecciones por Caliciviridae , Diarrea , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Leche Humana , Norovirus , Animales , Ratones , Ácidos y Sales Biliares/metabolismo , Infecciones por Caliciviridae/metabolismo , Infecciones por Caliciviridae/virología , Leche Humana/virología , Leche Humana/metabolismo , Diarrea/virología , Diarrea/metabolismo , Femenino , Humanos , Ratones Endogámicos C57BL

RESUMEN

There are four genogroups and 18 genotypes of human sapoviruses (HuSaVs) responsible for acute gastroenteritis. To comprehend their antigenic and virological differences, it is crucial to obtain viral stocks of the different strains. Previously, we utilized the human duodenum-derived cell line HuTu80, and glycocholate, a conjugated bile acid, to replicate and propagate GI.1, GI.2, and GII.3 HuSaVs (H. Takagi et al., Proc Natl Acad Sci U S A 117:32078-32085, 2020, https://10.1073/pnas.2007310117). First, we investigated the impact of HuTu80 passage number on HuSaV propagation. Second, we demonstrated that taurocholate improved the initial replication success rate and viral RNA levels in fecal specimens relative to glycocholate. By propagating 15 HuSaV genotypes (GI.1-7, GII.1-5, -8, and GV.1-2) and accomplishing preparation of viral stocks containing 1.0 × 109 to 3.4 × 1011 viral genomic copies/mL, we found that all strains required bile acids for replication, with GII.4 showing strict requirements for taurocholate. The deduced VP1 sequences of the viruses during the scale-up of serial passaged virus cultures were either identical or differed by only two amino acids from the original sequences in feces. In addition, we purified virions from nine strains of different genotypes and used them as immunogens for antiserum production. Enzyme-linked immunosorbent assays (ELISAs) using rabbit and guinea pig antisera for each of the 15 strains of different genotypes revealed distinct antigenicity among the propagating viruses across genogroups and differences between genotypes. Acquisition of biobanked viral resources and determination of key culture conditions will be valuable to gain insights into the common mechanisms of HuSaV infection. IMPORTANCE: The control of human sapovirus, which causes acute gastroenteritis in individuals of all ages, is challenging because of its association with outbreaks similar to those caused by human norovirus. The establishment of conditions for efficient viral propagation of various viral strains is essential for understanding the infection mechanism and identifying potential control methods. In this study, two critical factors for human sapovirus propagation in a conventional human duodenal cell line were identified, and 15 strains of different genotypes that differed at the genetic and antigenic levels were isolated and used to prepare virus stocks. The preparation of virus stocks has not been successful for noroviruses, which belong to the same family as sapoviruses. Securing virus stocks of multiple human sapovirus strains represents a significant advance toward establishing a reliable experimental system that does not depend on limited virus-positive fecal material.

Asunto(s)

Infecciones por Caliciviridae , Duodeno , Genotipo , Sapovirus , Replicación Viral , Sapovirus/genética , Humanos , Duodeno/virología , Duodeno/inmunología , Línea Celular , Animales , Infecciones por Caliciviridae/virología , Infecciones por Caliciviridae/inmunología , Gastroenteritis/virología , Antígenos Virales/inmunología , Antígenos Virales/genética , Heces/virología , Conejos , Cobayas , Variación Genética , ARN Viral/genética , Cultivo de Virus , Ácidos y Sales Biliares

RESUMEN

A new form of the rabbit haemorrhagic disease virus, RHDV2, first observed in European rabbits, has spread widely among different species of hares in Europe, jackrabbits and cottontails in North America, and hares in southern Africa. However, only limited surveillance studies have been undertaken so far. It is suggested that methods developed for controlling the disease in farmed rabbits in Europe and studying the efficacy of RHDV as a biological control agent in Australia could facilitate epidemiological research on those recently affected lagomorph species. This would enable the assessment of the risk of RHDV2 to native lagomorphs, including endangered species, and the determination of the main host species of RHDV2. Because RHDV2 has not spread equally through all lagomorph species, epidemiological studies could give insights into factors important for determining host susceptibility.

Asunto(s)

Infecciones por Caliciviridae , Especies en Peligro de Extinción , Virus de la Enfermedad Hemorrágica del Conejo , Animales , Virus de la Enfermedad Hemorrágica del Conejo/genética , África Austral/epidemiología , Infecciones por Caliciviridae/veterinaria , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología , América del Norte/epidemiología , Lagomorpha/virología , Conejos , Liebres/virología

RESUMEN

An intrinsically disordered protein (IDP) or region (IDR) lacks or has little protein structure but still maintains function. This lack of structure creates flexibility and fluidity, allowing multiple protein conformations and potentially transient interactions with more than one partner. Caliciviruses are positive-sense ssRNA viruses, containing a relatively small genome of 7.6-8.6 kb and have a broad host range. Many viral proteins are known to contain IDRs, which benefit smaller viral genomes by expanding the functional proteome through the multifunctional nature of the IDR. The percentage of intrinsically disordered residues within the total proteome for each calicivirus type species can range between 8 and 23%, and IDRs have been experimentally identified in NS1-2, VPg and RdRP proteins. The IDRs within a protein are not well conserved across the genera, and whether this correlates to different activities or increased tolerance to mutations, driving virus adaptation to new selection pressures, is unknown. The function of norovirus NS1-2 has not yet been fully elucidated but includes involvement in host cell tropism, the promotion of viral spread and the suppression of host interferon-λ responses. These functions and the presence of host cell-like linear motifs that interact with host cell caspases and VAPA/B are all found or affected by the disordered region of norovirus NS1-2. The IDRs of calicivirus VPg are involved in viral transcription and translation, RNA binding, nucleotidylylation and cell cycle arrest, and the N-terminal IDR within the human norovirus RdRP could potentially drive liquid-liquid phase separation. This review identifies and summarises the IDRs of proteins within the Caliciviridae family and their importance during viral replication and subsequent host interactions.

Asunto(s)

Caliciviridae , Proteínas Intrínsecamente Desordenadas , Proteínas Virales , Caliciviridae/genética , Caliciviridae/química , Humanos , Proteínas Virales/genética , Proteínas Virales/metabolismo , Proteínas Virales/química , Proteínas Intrínsecamente Desordenadas/química , Proteínas Intrínsecamente Desordenadas/metabolismo , Proteínas Intrínsecamente Desordenadas/genética , Genoma Viral , Infecciones por Caliciviridae/virología , Animales , Proteoma , Replicación Viral

RESUMEN

Introduction: Noroviruses are one of the most common causes of gastroenteritis in all age groups, including children. However, little has been reported on the transmission of norovirus within childcare facilities and the subsequent impact at the household level. Methods: We conducted an outbreak investigation of norovirus gastroenteritis in Central Queensland, Australia during May 2021, in a childcare facility and the associated exposed households. Case definitions and outbreak management were employed as per the Communicable Disease Network Australia guidelines for norovirus and suspected viral gastroenteritis. Each case or carer and respective household member was interviewed to determine the date and time of symptom onset, health outcomes, and infector-infectee pairs. We estimated attack rates within the childcare facility and households, and basic reproductive number (R0) for norovirus using time-dependent methods. Results: A total of 41 people developed gastrointestinal symptoms as a result of this outbreak, with 25 cases (61%) acquiring the infection in the centre and 16 cases (39%) occurring at households. Serial intervals were estimated as a mean 2.4 days (standard deviation 1.7 days), with a majority of cases (73%) in children under two years of age within the centre. Three faecal specimens were obtained, all detecting norovirus genotype II. The time-dependent R0 was 1.5 (95% confidence interval [95% CI]: 1.0-2.2). Discussion: The attack rate within the childcare facility was highest amongst children aged less than 2 years, highlighting the risk of infection for this age group. We recommend the exclusion of asymptomatic household contacts from childcare facilities to reduce the length and severity of norovirus outbreaks. Further investigation into childcare facility risk factors and associated households are required to optimise public health interventions.

Asunto(s)

Infecciones por Caliciviridae , Brotes de Enfermedades , Composición Familiar , Gastroenteritis , Norovirus , Humanos , Gastroenteritis/epidemiología , Gastroenteritis/virología , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología , Queensland/epidemiología , Norovirus/genética , Preescolar , Femenino , Masculino , Lactante , Niño , Adulto , Guarderías Infantiles , Adolescente , Heces/virología , Persona de Mediana Edad

RESUMEN

OBJECTIVES: Vaccinations should only be given to healthy cats, and deworming before vaccination is generally recommended; however, so far, no study has investigated the influence of intestinal parasitic infection on the immune response in kittens. The aim of this prospective study was to compare the antibody response to feline panleukopenia virus (FPV) vaccination in kittens with and without intestinal parasites. METHODS: Overall, 74 healthy kittens were included. Of these, 17 had intestinal parasites (12/17 Toxocara cati, 6/17 Cystoisospora felis, 1/17 Capillaria species). Both kittens with and without (n = 57) parasites received two primary kitten vaccinations with modified live FPV vaccines in a 4-week interval starting at the age of 8-12 weeks. Anti-FPV antibodies were determined at the beginning of the study (week 0) and at week 8 (4 weeks after the second vaccination) by haemagglutination inhibition. A ⩾four-fold titre increase (week 8 vs week 0) was defined as a response to vaccination. Comparison of the immune response in the kittens with and without intestinal parasites was performed using Pearson's χ2 test. RESULTS: Pre-vaccination antibodies were present in 4/17 (23.5%) kittens with intestinal parasites and in 24/57 (42.1%) without parasites. A ⩾four-fold titre increase was seen in 13/17 (76.5%) kittens with parasites compared with 32/57 (56.1%) kittens without parasites. There was neither a significant difference in pre-vaccination antibodies (P = 0.17), nor in vaccination response (P = 0.13) between kittens with and without parasites. CONCLUSIONS AND RELEVANCE: The results indicate that asymptomatic intestinal infections with endoparasites do not interfere with the immune response to kitten vaccination series. Parasitic infection (at least with T cati, C felis and Capillaria species) is therefore not a reason to postpone important vaccinations.

Asunto(s)

Anticuerpos Antivirales , Virus de la Panleucopenia Felina , Panleucopenia Felina , Parasitosis Intestinales , Vacunas Virales , Animales , Gatos , Virus de la Panleucopenia Felina/inmunología , Panleucopenia Felina/prevención & control , Panleucopenia Felina/inmunología , Parasitosis Intestinales/veterinaria , Parasitosis Intestinales/prevención & control , Parasitosis Intestinales/inmunología , Anticuerpos Antivirales/sangre , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Masculino , Vacunación/veterinaria , Femenino , Enfermedades de los Gatos/prevención & control , Enfermedades de los Gatos/inmunología , Enfermedades de los Gatos/parasitología , Enfermedades de los Gatos/virología , Estudios Prospectivos , Infecciones por Caliciviridae/veterinaria , Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/inmunología

RESUMEN

Fucosyltransferase 2 (FUT2) gene, which regulates the formation of Histoblood group antigens, could determine the human susceptibility to norovirus. This study aimed to investigate the correlation between FUT2 gene polymorphism and susceptibility to norovirus gastroenteritis in Han Chinese population. A total of 212 children patients with acute gastroenteritis were enrolled. The stool and serum samples were collected respectively. We used the qPCR method to detect the norovirus infection status from the stool samples, and we used serum samples to detect the FUT2 polymorphism. A case-control study was conducted to investigate the three common SNPs polymorphisms (rs281377, rs1047781, and rs601338) of FUT2 gene with sanger sequencing method. The results indicated that the homozygous genotypes and mutant allele of rs1047781 (A385T) would downgrade the risk of norovirus gastroenteritis in Chinese Han population (AA vs. TT, odds ratio [OR] = 0.098, 95% confidence interval [CI] = 0.026-0.370, p = 0.001; AA + AT vs. TT, OR = 0.118. 95% CI = 0.033-0.424, p = 0.001; A vs. T, OR = 0.528, 95% CI = 0.351-0.974, p = 0.002). There were no significant difference of rs281377 (C357T) and rs601338 (G428A) polymorphisms between norovirus positive and norovirus negative groups (p > 0.05). The haplotype T-T-G was less susceptible (OR = 0.49, 95% CI = 0.31-0.79, p = 0.0034) to norovirus infection compared to other haplotypes. Our results investigated the relationship between the FUT2 gene polymorphisms and norovirus susceptibility in Han Chinese population, and firstly revealed that children with homozygous genotypes and mutant alleles of FUT2 rs1047781 (A385T) were less susceptible to norovirus gastroenteritis.

Asunto(s)

Pueblo Asiatico , Infecciones por Caliciviridae , Fucosiltransferasas , Galactósido 2-alfa-L-Fucosiltransferasa , Gastroenteritis , Predisposición Genética a la Enfermedad , Genotipo , Norovirus , Polimorfismo de Nucleótido Simple , Humanos , Fucosiltransferasas/genética , Infecciones por Caliciviridae/genética , Infecciones por Caliciviridae/virología , Infecciones por Caliciviridae/epidemiología , Femenino , Masculino , Gastroenteritis/virología , Gastroenteritis/genética , Estudios de Casos y Controles , Preescolar , Norovirus/genética , Pueblo Asiatico/genética , Lactante , China/epidemiología , Niño , Heces/virología , Alelos , Haplotipos , Pueblos del Este de Asia

RESUMEN

BACKGROUND: Norovirus is the predominant pathogen causing foodborne illnesses and acute gastroenteritis (AGE) outbreaks worldwide, imposing a significant disease burden. This study aimed to investigate the epidemiological characteristics and genotypic diversity of norovirus outbreaks in Hongshan District, Wuhan City. METHODS: A total of 463 AGE cases from 39 AGE-related outbreaks in Hongshan District between January 1, 2021, and June 30, 2023, were included in the study. Reverse transcription-polymerase chain reaction (RT-PCR) was used to identify norovirus types GI and GII in anal swab samples from all cases. Norovirus-positive samples were sequenced and analyzed for the open reading frame (ORF) 1/ORF2 hinge region. RESULTS: 26 norovirus infectious outbreaks were reported among 39 acute diarrheal outbreaks, including 14 outbreaks in kindergartens, 8 in elementary schools, and 4 in universities. Based on clinical symptoms and epidemiological investigations, a total of 1295 individuals were identified as having been exposed to norovirus, yielding an attack rate of 35.75 %. A higher proportion of outbreaks was observed during the winter and spring seasons (38.46 %). Additionally, norovirus-positive samples were subjected to sequencing and analysis of the open reading frame (ORF) 1/ORF2 hinge region. Genotypic data for norovirus was successfully obtained from 18 (69.23 %) of the infectious outbreaks, revealing 10 distinct recombinant genotypes. GII.4 Sydney 2012 [P31] and GII.17[P17] were the predominant strains in 2021 and 2022, GII.3 [P12] emerged as the dominant strain in 2023. CONCLUSION: Norovirus outbreaks in Hongshan District predominantly occurred in crowded educational institutions, with peaks in the cold season and a high attack rate in universities. GII.3 [P12] has become the locally predominant strain.

Asunto(s)

Infecciones por Caliciviridae , Brotes de Enfermedades , Gastroenteritis , Variación Genética , Genotipo , Norovirus , Humanos , Norovirus/genética , Norovirus/clasificación , Norovirus/aislamiento & purificación , Gastroenteritis/virología , Gastroenteritis/epidemiología , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología , China/epidemiología , Niño , Masculino , Femenino , Preescolar , Adolescente , Adulto , Adulto Joven , Filogenia , Lactante , Estaciones del Año , Persona de Mediana Edad , Epidemias

RESUMEN

Norovirus (NoV) infection is a major cause of gastroenteritis worldwide. The virus poses great challenges in developing vaccines with broad immune protection due to its genetic and antigenic diversity. To date, there are no approved NoV vaccines for clinical use. Here, we aimed to develop a broad-acting quadrivalent NoV vaccine based on a chimpanzee adenovirus vector, AdC68, carrying the major capsid protein (VP1) of noroviral GI and GII genotypes. Compared to intramuscular (i.m.), intranasal (i.n.), or other prime-boost immunization regimens (i.m. â€‹+ â€‹i.m., i.m. â€‹+ â€‹i.n., i.n. â€‹+ â€‹i.m.), AdC68-GI.1-GII.3 (E1)-GII.4-GII.17 (E3), administered via i.n. â€‹+ â€‹i.n. induced higher titers of serum IgG antibodies and higher IgA antibodies in bronchoalveolar lavage fluid (BALF) and saliva against the four homologous VP1s in mice. It also significantly stimulated the production of blocking antibodies against the four genotypes. In response to re-stimulation with virus-like particles (VLP)-GI.1, VLP-GII.3, VLP-GII.4, and VLP-GII.17, the quadrivalent vaccine administered according to the i.n. â€‹+ â€‹i.n. regimen effectively triggered specific cell-mediated immune responses, primarily characterized by IFN-γ secretion. Furthermore, the preparation of this novel quadrivalent NoV vaccine requires only a single recombinant adenovirus to provide broad preventive immunity against the major GI/GII epidemic strains, making it a promising vaccine candidate for further development.

Asunto(s)

Adenoviridae , Anticuerpos Antivirales , Infecciones por Caliciviridae , Vectores Genéticos , Ratones Endogámicos BALB C , Norovirus , Pan troglodytes , Vacunas Virales , Animales , Norovirus/inmunología , Norovirus/genética , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Ratones , Infecciones por Caliciviridae/prevención & control , Infecciones por Caliciviridae/inmunología , Vacunas Virales/inmunología , Vacunas Virales/genética , Vacunas Virales/administración & dosificación , Vectores Genéticos/genética , Vectores Genéticos/inmunología , Adenoviridae/genética , Adenoviridae/inmunología , Femenino , Proteínas de la Cápside/genética , Proteínas de la Cápside/inmunología , Inmunoglobulina G/sangre , Gastroenteritis/prevención & control , Gastroenteritis/virología , Gastroenteritis/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Inmunoglobulina A/sangre , Genotipo , Saliva/inmunología , Saliva/virología , Líquido del Lavado Bronquioalveolar/inmunología , Líquido del Lavado Bronquioalveolar/virología

RESUMEN

Norovirus is an important etiologic agent of acute gastroenteritis and has become even more relevant in Brazil after the implementation of the monovalent rotavirus vaccine in 2006 through the public health system, now representing a significant portion of the etiology of acute diarrheal diseases. Although diagnosing acute gastroenteritis caused by norovirus is a relatively simple process, and the infection tends to be self-limited, the virus can be considerably harmful to vulnerable populations, such as children, the elderly, and immunocompromised individuals. The spread of norovirus is also particularly favorable among such groups due to its mode of transmission, favored by cluttered environments such as in hospitals and densely populated regions. Additionally, norovirus' ability to spread through water and food creates the need for measures to ensure adequate sanitation and the development of effective measures to prevent outbreaks and severe manifestations of the disease. This review aims to address the main reports of human norovirus detected in Brazil over the years, focusing on clinical-hospital, food-related, and urban conglomerate contexts, including the circulating strains.

Asunto(s)

Infecciones por Caliciviridae , Gastroenteritis , Norovirus , Norovirus/genética , Norovirus/aislamiento & purificación , Norovirus/clasificación , Brasil/epidemiología , Humanos , Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología , Gastroenteritis/virología , Gastroenteritis/epidemiología , Brotes de Enfermedades