Patagonian shellfish and hidden threats: unveiling the viral landscape and the first quantitative microbial risk assessment of Argentine bivalve mollusks.

Evaluation of two commercial multiplex RT-PCR tests for broad genotypic detection of viral gastroenteritis.

Molecular insights into viral agents of acute gastroenteritis detected among under five children in Assam, India.

ABSTRACT Commensal bacteria have been a centerpiece for understanding interkingdom impacts on viral replication. Multiple groups have investigated the roles commensal bacteria played in regulating enteric virus infection and it has been found that the mechanisms through which this regulation occurs varies between the viruses and bacteria explored. For noroviruses, commensal bacteria enhance or suppress viral infection in a region-dependent manner. Recently, it was found that the extracellular vesicles (EVs) produced by commensal bacteria can suppress norovirus infection. In this study, we used murine norovirus (MNV) to probe the immunological mechanisms induced by bacterial EVs. Global analysis of gene expression pointed to induction of cytosolic DNA pathways; thus, we evaluate the DNA content packaged within the bacterial EVs and DNA-sensing pathways that activate type I interferons (IFN), including STING and TLR9. Our results showed that loss of sting or tlr9, significantly decreased IFNβ production and recovered MNV replication in the presence of bEVs. Collectively, these data demonstrated bEVs of certain gram-negative bacteria can initiate antiviral DNA-mediated type I IFN production pathways and that these pathways are involved in the suppression of MNV replication. These findings expose novel mechanisms through which the native microbiota aids the host in controlling an enteric viral infection and offers a fresh perspective on interkingdom host‒microbiota interactions.

Aptamer (Apt)-based biosensors are promising tools for resource-limited Norovirus (NoV), where GII.4 is the predominant sub-genotype causing human infections. Considering their urgent and strict needs of on-site renewal, we present a smart regeneration strategy, inspired by the modern electronics industry, on a homemade screen-printed electrode (SPE). Aqueously prepared MXene@MWCNTs-Au-Fc (MWCNTs: multiwalled carbon nanotubes; Fc: ferrocene) and single-strand DNA (ssDNA), semi-complementary to NoV Apt, are permanently assembled onto the SPE. By incubating Apt and methylene blue (MB), Apt-ssDNA structures with MB filling are obtained. NoV competitively combines Apt, dissociates Apt-ssDNA structures, and triggers ratiometric ΔIMB/IFc. Remarkably, a programmable thermal profile is written into a micro controller unit (MCU) of the SPE. With on-chip hardware resources as the heater, error amplifier, and heater driver, the temperature curve is sectionally regulated during Apt-ssDNA regeneration, concurrently promoting reaction and preventing functionalization deterioration. Besides the wide range (1-106 copies mL-1) and impressive limit of detection (0.67 copies mL-1), this method shows significantly less IMB loss than control (98.67% vs 80.26%). For NoV-contaminated beef and pork, the proposed results meet well with certified RT-qPCR (RSDs < 4.89%).

A novel efficient pretreatment device integrated with chitosan aerogel and hydrogel composite membrane for detection of norovirus in seafood.

Human norovirus (HNoV) is a major cause of gastroenteritis worldwide, for which no antiviral therapies exist to date. Previously, our lab has demonstrated that both HNoV and murine norovirus (MNV1) are highly dependent on the expression of the Ras-GTPase-activating protein-binding protein 1 (G3BP1), a cellular protein mostly involved in the assembly of stress granules. We, therefore, hypothesize that targeting G3BP1 could be a promising antiviral strategy against noroviruses. Here, we designed a proof-of-concept study to test targeted protein degradation as a mechanism to induce the specific proteolysis of G3BP1 via the proteasome. To do so, we generated a cellular platform for the overexpression of G3BP1 fused to the bacterial protein Halotag (HaloG3BP1). First, we showed that MNV1 replication is restored in G3BP1-knockout (ΔG3BP1) cells complemented with HaloG3BP1. We then used a PROteolysis TArgeting Chimera (PROTAC) directed toward the Halotag (HaloPROTAC) to induce the specific degradation of HaloG3BP1. We further demonstrate that proteolysis of G3BP1 reduces MNV1 replication, leading to a lower infectious virus yield and preventing virus-induced cell death. We also confirmed that the mechanism of HaloPROTAC3 is mediated via the recruitment of Cullin2-VHL E3-ubiquitin ligase. Our findings add to the body of evidence supporting that targeting of the cellular protein G3BP1 can be used as an antiviral approach and validates the use of PROTACs for the efficient and specific degradation of cellular factors as a feasible methodology to combat viral diseases.

Norovirus is the leading cause of medically attended acute gastroenteritis in the United States. Efforts to reduce the disease burden are constrained by uncertainty around fundamental aspects of norovirus epidemiology. This study describes characteristics of norovirus infections and explores potential risk factors for symptomatic infections in early life. The Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal birth cohort study followed 245 children from birth to 2 years of age with weekly stool sample collection and symptom surveys. Stool samples were tested by reverse transcriptase-realtime polymerase chain reaction to detect norovirus genogroup (G)I and GII; positive samples were genotyped. Infections accompanied by diarrhea and/or vomiting were considered symptomatic. Children were categorized as adherent if they participated for ≥18 months and submitted ≥70% of samples. A total of 72 GI and 330 GII norovirus infections (among 156 children) were identified. One-fifth (20.8%) of adherent children experienced ≥1 norovirus infection by 6 months of age, increasing to 84.2% children by 2 years of age. About one-third of infections were symptomatic, including half of infections with cycle threshold values <25. Infection with norovirus genotype GII.4 Sydney was the strongest predictor of symptomatic infection in adjusted analyses, as was older age and higher viral load. Childcare attendance, breastfeeding, mother's secretor status, and prior infections were not predictive of symptom status. This study highlights fundamental characteristics of norovirus epidemiology in early life with implications for understanding the full natural history of the disease, disease transmission and prevention approaches.

Background/Objectives: Viral gastroenteritis leads to a broad range of hospitalization costs globally in children, depending on the region. To our knowledge, no recent studies have examined the hospitalization cost associated with viral gastroenteritis in Romania. The aim of this study is to determine the direct hospitalization cost of community-acquired viral gastroenteritis (rotavirus, adenovirus and norovirus) in children admitted to Children’s Clinical Hospital of Brașov, Romania, for one year. Methods: All children aged 0–60 months hospitalized for a stool sample positive for rotavirus, adenovirus or norovirus during January 2023 and December 2023 were included in this study. Hospital-acquired gastroenteritis, gastrointestinal coinfections or children with acute coinfection were excluded. The stool specimens were tested using the immunochromatography method. Results: Out of the total of 282 children, 218 children presented rotavirus gastroenteritis, 35 children presented adenovirus gastroenteritis and 29 children presented norovirus gastroenteritis. Regarding patient characteristics, a higher proportion of boys than girls was observed in all three comparison groups, the average age for children with rotavirus was 22.2 months vs. norovirus and adenovirus, and children presented an average age of 16.4 months. Average hospitalization length of stay for rotavirus was 4.64 (±1.95) days, for adenovirus it was 4.54 (±1.52) days and for norovirus it was 4.75 (±1.93) days. Direct hospitalization costs did not differ between rotavirus, adenovirus, and norovirus infections (Kruskal–Wallis H(2) = 0.145, p = 0.930). Conclusions: In this single-center study, rotavirus remained the most frequent cause of viral gastroenteritis requiring hospitalization in young children, followed by adenovirus and norovirus. Although the average length of stay was similar across groups, hospitalization costs varied, with rotavirus-associated cases showing the highest mean expenses and widest cost variability.

The aim is to address the limitations of clinical surveillance-specifically, its high cost and underreporting of asymptomatic infections and untreated individuals-by implementing municipal wastewater surveillance. This study characterizes the epidemiological dynamics of Norovirus (NoV) and Rotavirus A (RVA) in Yantai City and evaluates the effectiveness of Wastewater-Based Epidemiology (WBE) for early outbreak warning. From 2023 to 2024, weekly wastewater samples (1-2 samples per site) were collected from 10 municipal wastewater treatment plants (WWTPs) across five urban districts and three counties in Yantai City. Following concentration via polyethylene glycol (PEG) precipitation, viral nucleic acids of NoV GI/GII and RVA were examined using multiplex reverse transcription quantitative PCR (RT-qPCR), with quantification based on standard curves. Cross-correlation analysis was applied to assess time-lag relationships between viral concentrations in wastewater and clinical case peaks, and to evaluate the statistical significance (α = 0.05) of the early warning time window. Wastewater surveillance (no. samples: 1,391) identified NoV GII as the dominant virus with an overall detection rate of 85.84%. However, from 2023 to 2024, its annual detection rate declined significantly from 92.27% to 73.81% (P < 0.001). During the same period, NoV GI also declined annually from 83.55% to 69.07% (P < 0.001), whereas RVA detection increased substantially by 145.7% annually, rising from 26.6% to 65.36% (P < 0.001). NoV peaked in winter-spring seasons (GI: 76.61% in winter, 89.20% in spring; GII: 87.13% in winter, 91.31% in spring), whereas RVA peaked in spring (42.72%) and summer (55.79%). Seasonal fluctuation intensity followed this order: RVA (χ2 = 69.07) > NoV GI (χ2 = 49.28) > NoV GII (χ2 = 21.44). Cross-correlation analysis indicated that NoV GII concentration in wastewater peaked 1 month ahead of clinical cases, showing significant positive correlations with both reported cases (r = 0.60, P = 0.002) and clinical positivity rates (r = 0.53, P = 0.009) at a one-month lag. A one-month lag for NoV GI and a two-month lag for RVA relative to clinical cases were observed but were not statistically significant (P > 0.05). Systematic wastewater surveillance effectively captured population-level epidemiological dynamics of NoV and RVA. Notably, NoV GII provided a significant one-month early warning signal (P < 0.01), establishing its value as a leading indicator for diarrheal virus prevention and control in Yantai City.

ABSTRACT Human astroviruses are a common cause of viral gastroenteritis and are often underdiagnosed. While infections are typically mild or asymptomatic in immunocompetent hosts, astrovirus can cause prolonged and severe disease in immunocompromised individuals. Here, we conducted a case-control study to evaluate the clinical presentation of astrovirus infections in paediatric oncology patients. Our findings were compared to two groups: (1) norovirus infections in the same immunocompromised cohort, and (2) a cohort of immunocompetent children with and without diarrheal symptoms. Astrovirus was detected in 9.8% of immunocompromised patients, with prolonged shedding seen in multiple cases. Astrovirus infection was associated with an increased odds of diarrhoea, although this association weakened when adjusting for co-infections. In contrast, norovirus was not significantly associated with diarrhoea in immunocompromised patients, despite prolonged shedding in 24% of the cohort. High rates of co-infection with adenovirus and Clostridium difficile may have influenced symptom patterns. In the immunocompetent cohort, astrovirus was not associated with diarrhoea, while norovirus showed a strong association with symptoms. These findings indicate that astrovirus infections are more likely to cause diarrhoea in immunocompromised paediatric patients, while often asymptomatic in immunocompetent children. Norovirus showed the opposite trend, highlighting distinct roles of host immune status in shaping clinical outcomes. These findings highlight the importance of considering astrovirus as a potential contributor to gastrointestinal symptoms in immunocompromised children and call for broader diagnostic testing and further research on viral co-infections and persistence.

Norovirus infection control in Korea: points to consider.

BackgroundThe ongoing ‘Observational Research on the Impact and Outcomes of Norovirus’ (ORION) study is a prospective, community-based cohort study of acute gastroenteritis (AGE), and specifically norovirus (NoV) gastroenteritis (NGE), burden among adults with underlying medical conditions who may be at higher risk for severe NGE.MethodsFrom January–March 2025, we recruited adults (≥18 years) with pre-specified “high-risk” medical conditions [e.g., cardiovascular disease, gastrointestinal (GI) or immunocompromising (IC) conditions] and otherwise healthy controls from 4 Kaiser Permanente (KP) sites. Study participants report new onset of AGE weekly, defined as ≥1 vomiting episode and/or ≥3 diarrhea episodes in a 24-hour period. Participants with AGE: (1) complete surveys about illness severity, quality of life impacts, and exacerbation of underlying conditions and (2) self-collect stool specimens for multiplex GI pathogen testing. Here we report AGE episodes per 100 person-weeks (PW) and laboratory testing results through April 2025. Participant observation continues through December 2025.ResultsWe enrolled 3,527 participants across the 4 sites, described in Table 1. Participants reported 525 AGE episodes over 15,329 PWs (incidence of 3.4/100 PW). AGE incidence peaked around 5-7/100 PWs in January/February and declined in March/April. Among participants with AGE (Table 2), most were female (66%) and either 35-49 years (36%) or 50-64 years (24%); 41% had IC conditions, 34% had GI conditions; 34% had obesity, and only 6% were otherwise healthy. Six AGE episodes involved hospitalization. In 325 stool specimens tested to date, 30% (n=98) had ≥1 pathogen detected and 5% (n=15) were NoV-positive (Table 3), with genotype GII comprising 87% of NoV-positive specimens.ConclusionBurden of NGE in individuals with underlying medical conditions is not well understood and is often extrapolated from studies of medically attended AGE, which underestimate community disease burden. ORION will provide valuable AGE and NGE burden estimates from the community setting and allow for improved assessment of disease severity for adults with high-risk underlying medical conditions.DisclosuresMark A. Schmidt, PhD, MPH, AstraZeneca: Grant/Research Support|HilleVax: Grant/Research Support|Janssen: Grant/Research Support|Moderna: Grant/Research Support Holly C. Groom, MPH, AstraZeneca: Grant/Research Support|Moderna: Grant/Research Support Jennifer L. Kuntz, MS, PhD, Astra Zeneca: Grant/Research Support|Moderna, Inc.: Grant/Research Support|Pfizer: Grant/Research Support Claudia Steiner, PhD, Moderna, Inc: Grant/Research Support Michael J. Miller, DrPH, American Journal of Health-System Pharmacy: Honoraria|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|The American Society of Health-System Pharmacists, Inc: Grant/Research Support Lisa Jackson, MD, MPH, Moderna: Grant/Research Support Jennifer K. Meece, PhD, CSL Seqirus: Grant/Research Support|GSK: Grant/Research Support|ModernaTX: Grant/Research Support John F. Dickerson, PhD, AstraZeneca: Grant/Research Support|HilleVax: Grant/Research Support|Moderna: Grant/Research Support Michelle Blake, PhD, MSc, HBSc, Moderna: Employment|Moderna: Stocks/Bonds (Public Company) Christine Kim, PhD, MSPH, Director, Moderna, Inc.: Employee|Director, Moderna, Inc.: Stocks/Bonds (Public Company) Wen-Hsing Wu, MS, Moderna: Stocks/Bonds (Public Company) Carly A. Crocker, BS, Moderna: Employment|Moderna: Stocks/Bonds (Public Company) Brandon J. Patterson, PharmD, PhD, Moderna: Employment|Moderna: Stocks/Bonds (Private Company) Meklit Workneh, MD, MPH, Moderna: Stocks/Bonds (Public Company) Lee Quist, DO, MBA, Moderna: Stocks/Bonds (Public Company) Katherine B. Carlson, PhD, MPH, Moderna: Employee|Moderna: Stocks/Bonds (Private Company)

BackgroundNorovirus gastroenteritis (NGE) is the leading cause of acute gastroenteritis (AGE) in the US but often undiagnosed due to limited clinical testing. Underlying medical conditions such as immunocompromising disorders increase the risk of severe outcomes from AGE and NGE and may exacerbate pre-existing conditions, worsening clinical outcomes. In this analysis, we estimated the association between underlying medical conditions and acute all-cause hospitalization among patients with medically attended AGE (MA-AGE) or MA-NGE.MethodsWe conducted a retrospective cohort study using Optum’s de-identified Clinformatics® Data Mart Database (Optum® CDM) of commercially insured and Medicare Advantage members. MA-AGE and MA-NGE episodes ≥ 14 days apart were identified via ICD-10 codes from July 1, 2022–June 30, 2024. Demographics and underlying medical conditions were identified in the year prior to index. Acute hospitalization was assessed within 3 days of index date. Generalized estimating equations adjusted for age, sex, and US Census region were used to calculate adjusted risk ratios (aRR) and 95% confidence intervals (95% CI) for associations with acute hospitalization.ResultsWe identified 1,785,834 and 6,252 MA-AGE and MA-NGE episodes, respectively. Over 60% occurred in adults ≥ 60 years and over 75% in individuals with ≥ 1 underlying condition (Figure 1). Acute hospitalization occurred in 11% of MA-AGE and 43% of MA-NGE episodes (Figure 2). Compared to those without underlying medical conditions, having ≥ 1 condition was associated with greater acute hospitalization risk [MA-AGE aRR (95% CI): 3.18 (3.11-3.23); MA-NGE: 2.83 (2.38-3.37)] (Figure 3, model 1). Risk further increased for individuals with ≥ 2 conditions (Figure 3, model 2).ConclusionUnderlying medical conditions were strongly associated with higher risk of acute hospitalization for AGE and NGE, even after adjusting for known risk factors including age and sex. These findings align with prior research and emphasize the need for enhanced prevention strategies, including vaccines, particularly for individuals with underlying medical conditions. Future work may explore analytic methods to account for underreporting of NGE cases in real-world data given diagnostic limitations.DisclosuresChristine Kim, PhD, MSPH, Director, Moderna, Inc.: Employee|Director, Moderna, Inc.: Stocks/Bonds (Public Company) John Shen, MSPH in Epidemiology, Moderna: Contracted Research Wen-Hsing Wu, MS, Moderna: Stocks/Bonds (Public Company) Elissa Wilker, ScD, AstraZeneca: Stocks/Bonds (Public Company)|Moderna: Salary|Moderna: Stocks/Bonds (Public Company) Brandon J. Patterson, PharmD, PhD, Moderna: Employment|Moderna: Stocks/Bonds (Private Company) Christopher Bush, MPH, Aetion, Inc.: Stocks/Bonds (Private Company) Ben Lopman, PhD, Epidemiological Research and Methods: Advisor/Consultant|Hillevax: Advisor/Consultant Daniel C. Payne, PhD, MSPH, Merck: Advisor/Consultant|Moderna: Advisor/Consultant Evan J. Anderson, MD, Moderna: Stocks/Bonds (Public Company) Katherine B. Carlson, PhD, MPH, Moderna: Employee|Moderna: Stocks/Bonds (Private Company)

Norovirus (NoV) and sapovirus (SaV) are major viral pathogens causing acute gastroenteritis (AGE) in both children and adults in developed countries and are also responsible for large-scale outbreaks. However, in Quebec, Canada, there are limited and updated data with respect to the genotypes circulating and implicated in outbreaks, particularly for SaV. This study aimed to investigate the genetic diversity and genotype predominance of NoVs and SaVs associated with AGE outbreaks in Quebec, Canada. Confirmed NoV and SaV outbreaks from long-term care facilities and hospital settings between September 2011 and April 2016 were investigated (n = 252). NoVs and SaVs were genetically diverse: 21 RdRp-capsid combinations were identified, of which 10 are recombinants. NoV GII.4 New Orleans[P4 NewOrleans] was the predominant genotype from 2011 to 2013, and GII.4 Sydney[P31] was the predominant genotype from 2013 to 2015. In 2015–2016, no single genotype predominated; instead, GII.17[P17], GII.4 Sydney[P16], GII.4 Sydney[P31], and SaV GI.2 strains were co-circulating at similar frequencies. Notably, emerging global genotypes including GII.17[P17], GII.4 Sydney[P16], GII.2[P16], and GII.4 San Francisco[P31] were detected for the first time in Quebec. These findings may contribute to an enhanced understanding of NoV and SaV infection and spread, and to the development of candidate vaccines.

Large norovirus GII.17 outbreak in a school in Northern Italy: A novel emerging sublineage within an emerging genotype?

Hospital-derived wastewater can enter the aquatic environment, posing a serious risk to public health due to the presence of pathogenic viruses and antimicrobial resistant (AMR) organisms. A quantitative understanding of the factors affecting the dispersal and fate of these pathogens in near-shore environments, remains poorly understood. Here we present a real-world exemplar that demonstrates how hydrodynamic modelling can quantify human exposure risk of wastewater-derived pathogens from three hospitals into coastal areas with high-risk receptors (recreational waters, tourist beaches, shellfisheries). The study focused on the dispersal and fate of norovirus (NoV) GI & GII and AMR genes along the freshwater-estuarine-marine continuum over a 1-year period to examine the impact of season, tidal patterns and pathogen loading rate. Our simulations predicted that combined sewer overflow discharges (CSOs) contributed 41% of the total hospital-derived viral load delivered to the coastal zone. Risk analysis revealed significant potential for local exceedances of NoV GI concentrations at designated bathing sites exceeding the infectious dosage threshold, reaching 59% probability in the summer months. The results highlight the significant role of hospital-derived wastewater, particularly during the summer months, coinciding with peak tourist activities and recreational water use. The study also suggested that the bioaccumulation of hospital-derived NoV and AMR in shellfish could pose a significant health risk to consumers. This research highlights the need to implement advanced treatment technologies, predictive water quality modelling, and regulatory adjustments to help protect the public from infectious agents present in hospital-derived wastewater released into the environment.

A 3D-printed, self-driven microfluidic sensor chip for point-of-care testing (POCT) of norovirus.

Young children are susceptible to infectious diseases due to their developing immune systems and close contact in group care settings. During the coronavirus disease 2019 (COVID-19) pandemic, infection prevention measures may have altered the epidemiology of common childhood infections, yet evidence on variations by facility type and region remains limited. In this study, the occurrence of COVID-19 and child-specific infectious diseases in childcare and early childhood education facilities in Japan was examined with particular focus on facility type and regional population density. A nationwide mail survey was conducted between January and April 2023 among 5,000 facility managers, and 710 valid responses were analysed. Over 90% of facilities reported at least one COVID-19 case within the previous year. The occurrence of child-specific infectious diseases, including adenovirus infection, hand, foot, and mouth disease, herpangina, streptococcal infection, norovirus infection, and respiratory syncytial virus infection, was lower in kindergartens serving children aged ≥ 3 years than in children in daycare centres or certified childcare centres (p < 0.05). Hand, foot, and mouth disease and influenza virus infection showed significant linear associations with population density, with lower reporting rates in less densely populated regions (p < 0.05). Conversely, rotavirus infection was more frequently reported in low-density regions (p < 0.05), whereas other child-specific infectious diseases exhibited heterogeneous and non-linear regional patterns, indicating that population density alone does not explain regional variation. These results highlight the importance of facility-, age-, and region-specific approaches to infection prevention in childcare settings beyond the COVID-19 pandemic.

The development of sensitive and high-throughput methods for detecting foodborne viruses is crucial for disease prevention and public health protection. In this study, we present a novel localized Cas13a-based DNA walker (LCas13a-DNA walker) for the ultrasensitive, stable, and rapid detection of norovirus (NoV). When the DNA walker was confined in AuNPs, the spatial confinement effect improved the local concentration of reaction substrates, accelerated the reaction speed, and enhanced the sensitivity of the DNA walker. Besides, an original design of uracil-rich hairpin (UH)-modified AuNPs as the walking track significantly improves the stability of the detection system. Meanwhile, employing CRISPR/Cas13a as the driving force streamlines viral RNA recognition and substantially reduces the reaction time down to 30 minutes by eliminating the reverse transcription step. Additionally, a biomimetic array, formed by photonic crystals (PCs), enabled high-throughput signal acquisition with a microplate reader, and concurrently amplified the fluorescence signal. The proposed assay realized ultra-sensitivity of NoV with a detection limit as low as 4.1 pM and a wide linear range from 10 pM to 5 nM. Due to the advantages of high sensitivity, high-throughput, stability, and rapid analysis, this proposed method provides a potential strategy for point-of-care detection of pathogenic viruses in food safety monitoring and disease diagnosis.