Viruses, Vol. 12, Pages 955: Evaluation of the 50% Infectious Dose of Human Norovirus Cin-2 in Gnotobiotic Pigs: A Comparison of Classical and Contemporary Methods for Endpoint Estimation

In this study, we evaluated the median infectious dose (ID50) and diarrhea dose (DD50) of the GII.4/2003 variant of HuNoV (Cin-2) in the gnotobiotic pig model of HuNoV infection and disease. Using various mathematical approaches (Reed–Muench, Dragstedt–Behrens, Spearman–Karber, exponential, approximate beta-Poisson dose–response models, and area under the curve methods), we estimated the ID50 and DD50 to be between 2400–3400 RNA copies, and 21,000–38,000 RNA copies, respectively. Contemporary dose–response models offer greater flexibility and accuracy in estimating ID50. In contrast to classical methods of endpoint estimation, dose–response modelling allows seamless analyses of data that may include inconsistent dilution factors between doses or numbers of subjects per dose group, or small numbers of subjects. Although this investigation is consistent with state-of-the-art ID50 determinations and offers an advancement in clinical data analysis, it is important to underscore that such analyses remain confounded by pathogen aggregation. Regardless, challenging virus strain ID50 determination is crucial for identifying the true infectiousness of HuNoVs and for the accurate evaluation of protective efficacies in pre-clinical studies of therapeutics, vaccines and other prophylactics using this reliable animal model.
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research

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S. Le Guyader Human noroviruses (NoV) cause epidemics of acute gastroenteritis (AGE) worldwide and can be transmitted through consumption of contaminated foods. Fresh products such as shellfish can be contaminated by human sewage during production, which results in the presence of multiple virus strains, at very low concentrations. Here, we tested a targeted metagenomics approach by deep-sequencing PCR amplicons of the capsid (VP1) and polymerase (RdRp) viral genes, on a set of artificial samples and on shellfish samples associated to AGE outbreaks, to evaluate its advantages and limitations in the identification of s...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research
Human noroviruses are the leading cause of epidemic and sporadic acute gastroenteritis worldwide and the most common cause of foodborne illness in the United States. Several natural compounds, such as aged-green tea extract (aged-GTE), have been suggested as ingestible antiviral agents against human norovirus based on data using murine norovirus and feline calicivirus as surrogates. However, in vitro data showing their effectiveness against infectious human norovirus are lacking. We tested the activity of aged-GTE to inhibit human norovirus in a human intestinal enteroids (HIEs) model and Tulane virus in LLC-monkey kidney ...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
In this study, we designed universal specific primers and an Exo probe to hybridize to all genetic clusters of NoVs GII based on the conserved region at the ORF1-ORF2 junction of the genome. For the first time, we established a rapid and reliable reverse transcription recombinase polymerase amplification (RT-RPA) method for the detection of NoVs GII within 20 min. This method can specifically amplify NoVs GII, and the detection limit was as low as 1.66×102 copies/μL. The method was validated in terms of LOD, accuracy, and specificity. We tested 55 real samples including foods, water, and feces. The results showed ...
Source: Analytical Biochemistry - Category: Biochemistry Authors: Tags: Anal Biochem Source Type: research
Human noroviruses (HuNoVs) are the cause of more than 95% of epidemic non-bacterial gastroenteritis worldwide, with some lethal cases. These viral agents affect people of all ages. However, young children and older adults are the highest-risk groups, being affected with the greatest rate of hospitalizations and morbidity cases. HuNoV structural proteins, especially VP1, have been studied extensively. In contrast, the functions of the non-structural proteins of the virus have been undescribed in depth. Studies on HuNoV non-structural proteins have mostly been made by expressing them individually in in vitro cultures, provid...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
ConclusionsEmployees in hospitals and community facilities seem quantitatively to be most vulnerable towards NoV epidemics. Therefore, high quality of prevention measures in these settings, respective compliance with prevention strategies should have the highest priority. The disease can be considered as an occupational disease, even regularly without long-term consequences. Following work safety rules, a vaccination for vulnerable groups should be recommended if the vaccine development turns out to be successful.
Source: International Archives of Occupational and Environmental Health - Category: Occupational Health Source Type: research
In this study, we analyzed the epidemiological and genetic features of NoV outbreaks from July 2014 to June 2018 in Huzhou, China. A total of 450 stool samples collected from 51 AGE outbreaks were tested for NoVs by real-time RT PCR. Partial polymerase and capsid sequences of NoV-positive samples were amplified and sequenced for phylogenetic analysis. NoVs were found to be responsible of 84.3% of AGE outbreaks in Huzhou over the past 5 years. Most NoV outbreaks were reported in the cool months (November-March) and occurred in primary schools and kindergartens. Changes in the diversity of genotypes and the distribution of p...
Source: Archives of Virology - Category: Virology Source Type: research
Authors: Hanisch FG, Aydogan C Abstract Norovirus infections belong to the most common causes of human gastroenteritis worldwide, and epidemic outbreaks are responsible for hundreds of thousands deaths annually. Strikingly, no antiviral treatment is available due to the difficulty in cultivating virions or in generating a vaccine, and due to the fact that their infection mechanisms are poorly understood. However, there is consent that noroviruses bind to histo-blood group antigens (HBGAs) on their way through the digestive tract. The HBGA profiles vary individually, making people more or less susceptible to differe...
Source: Nestlee Nutrition Institute Workshop Series - Category: Nutrition Tags: Nestle Nutr Inst Workshop Ser Source Type: research
This study used a nationally representative serum bank to estimate the seroprevalence to five norovirus genotypes including three GII variants: GI.1 Norwalk, GI.4, GII.3, GII.4 US95/96, GII.4 Farmington Hills, GII.4 New Orleans, and GIV.1 in the USA population (aged 16 to 49 years). Changes in seroprevalence to the three norovirus GII.4 variants between 1999 and 2000, as well as 2003 and 2004, were measured to examine the role of population immunity in the emergence of pandemic GII.4 noroviruses. The overall population-adjusted seroprevalence to any norovirus was 90.0% (1999 to 2000) and 95.9% (2003 to 2004). Seroprevalenc...
Source: Viruses - Category: Virology Authors: Tags: Article Source Type: research
Human noroviruses (HuNoVs) cause sporadic and epidemic outbreaks of gastroenteritis in all age groups worldwide. We previously reported that stem cell-derived human intestinal enteroid (HIE) cultures support replication of multiple HuNoV strains and that some strains (e.g., GII.3) replicate only in the presence of bile. Heat- and trypsin-treatment of bile...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: Biological Sciences Source Type: research
Noroviruses are a major cause of viral epidemic gastroenteritis in humans worldwide. The protease (Pro) encoded in open reading frame 1 (ORF1) is an essential enzyme for proteolysis of the viral polyprotein. Although there are some reports regarding the evolutionary analysis of norovirus GII-encoding genes, there are few reports focused on the Pro region. We analyzed the molecular evolution of the Pro region of norovirus GII using bioinformatics approaches. A time-scaled phylogenetic tree of the Pro region constructed using a Bayesian Markov chain Monte Carlo method indicated that the common ancestor of GII diverged from G...
Source: Frontiers in Microbiology - Category: Microbiology Source Type: research
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