Type III interferon (IFN), or IFN lambda (IFN-λ), is an essential component of the innate immune response to mucosal viral infections. In both the intestine and the lung, signaling via the IFN-λ ...receptor (IFNLR) controls clinically important viral pathogens, including influenza virus, norovirus, and rotavirus. While it is thought that IFN-λ cytokines are the exclusive ligands for signaling through IFNLR, it is not known whether genetic ablation of these cytokines phenotypically recapitulates disruption of the receptor. Here, we report the serendipitous establishment of
mice, which lack all known functional murine IFN-λ cytokines. We demonstrate that, like
mice lacking IFNLR signaling, these mice display defective control of murine norovirus, reovirus, and influenza virus and therefore genocopy
mice. Thus, for regulation of viral infections at mucosal sites of both the intestine and lung, signaling via IFNLR can be fully explained by the activity of known cytokines IFN-λ2 and IFN-λ3. Our results confirm the current understanding of ligand-receptor interactions for type III IFN signaling and highlight the importance of this pathway in regulation of mucosal viral pathogens.
Type III interferons are potent antiviral cytokines important for regulation of viruses that infect at mucosal surfaces. Studies using mice lacking the
gene encoding the type III interferon receptor have demonstrated that signaling through this receptor is critical for protection against influenza virus, norovirus, and reovirus. Using a genetic approach to disrupt murine type III interferon cytokine genes
and
, we found that mice lacking these cytokines fully recapitulate the impaired control of viruses observed in mice lacking
Our results support the idea of an exclusive role for known type III interferon cytokines in signaling via IFNLR to mediate antiviral effects at mucosal surfaces. These findings emphasize the importance of type III interferons in regulation of a variety of viral pathogens and provide important genetic evidence to support our understanding of the ligand-receptor interactions in this pathway.
NOROVIRUSES - A HIDDEN THREAT Stoyanova, Asya
Problems of infectious and parasitic diseases,
02/2022, Volume:
49, Issue:
3
Journal Article
Open access
Acute nonbacterial gastroenteritis is ubiquitous, and noroviruses are considered to be among the most common etiological agents. Noroviruses affect people of all ages. As a rule, infections caused by ...them are mild and self-limiting within 1-3 days but there is always a risk of a more severe course, especially in infants and the elderly. Being considered as mild and fast transient, noroviruses receive less attention than other infectious pathogens. The clinical and economic burden of norovirus gastroenteritis is often underestimated. Detection of the etiological role of noroviruses is essential not only from the clinical point of view, but also from the economic one because of the damage that norovirus infections cause to tourism and food industry. At present, prevention and counter disinfection measures are the only weapon against norovirus infections.
In this narrative review, results from a non-systematic search on the recent literature on noroviruses are presented. The review describes the basic biological characteristics of noroviruses, their genetic diversity and current classification, as well as the epidemiological aspects of the norovirus infection, its clinical manifestation, the diagnostic approaches, prevention and control measures and current state-of-the art for norovirus vaccine development.
Introduction. Human Noroviruses (HuNoV) are highly contagious pathogens responsible of acute human norovirus infection (HuNoVI). GII.4 is the prevailing norovirus genotype in the incidence of ...gastroenteritis worldwide. Currently there are no studies on the molecular monitoring and phylogenetic analysis of HuNoV in the territory of the Sverdlovsk region, therefore it is not possible to objectively assess their genetic diversity.
The aim of the study is to carry out genotyping and phylogenetic analysis of HNoVI in municipalities of the Sverdlovsk region: Ekaterinburg, Nizhny Tagil, Kamensk-Uralsky in 2022.
Materials and methods. Fecal samples were collected from children suffering from HuNoVI in the municipalities of the Sverdlovsk region. Viral RNA was extracted from stool samples followed by reverse transcription polymerase chain reaction with degenerate primers flanking the ORF1/ORF2 junction. The amplified samples were genotyped by Sanger sequencing. Multiple sequence alignments were carried out and phylogenetic trees were constructed.
Results. The total number of studied samples was 220. According to sequencing results, 73 positive sequences of HuNoV were typed, which represents 33% of the total volume of the studied samples. The largest share of genotypes is occupied by noroviruses GII (58%), noroviruses GI (42%). Noroviruses GII.17, GI.3 were the dominant genotypes. Phylogenetic analysis demonstrates that the identified sequences on the territory of the Sverdlovsk region have the smallest genetic distance, which gives grounds for their unification into a common cluster.
Conclusion. For the first time, a genetic analysis of HuNoV was carried out in the territory of the Sverdlovsk region. The norovirus genotyping system based on the amplification of the ORF1/ORF2 region makes it possible to successfully identify various genotypes of noroviruses from the Sverdlovsk region. It has been confirmed that GII noroviruses remain the dominant genetic group. The results of phylogenetic analysis demonstrate the greatest homology in the formed clusters between isolates from Ekaterinburg, Nizhny Tagil, Kamensk-Uralsky.
Human noroviruses (HuNoVs) are the leading etiological agent causing the worldwide outbreaks of acute epidemic non-bacterial gastroenteritis. Histo-blood group antigens (HBGAs) are commonly ...acknowledged as cellular receptors or co-receptors for HuNoVs. However, certain genotypes of HuNoVs cannot bind with any HBGAs, suggesting potential additional co-factors and attachment receptors have not been identified yet. In addition, food items, such as oysters and lettuce, play an important role in the transmission of HuNoVs. In the past decade, a couple of attachment factors other than HBGAs have been identified and analyzed from foods and microbiomes. Attachment factors exhibit potential as inhibitors of viral binding to receptors on host cells. Therefore, it is imperative to further characterize the attachment factors for HuNoVs present in foods to effectively control the spread of HuNoVs within the food chain. This review summarizes the potential attachment factors/receptors of HuNoVs in humans, foods, and microbiome.
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•Certain genotypes of HuNoVs do not exhibit a binding affinity to any HBGAs.•Some non-HBGAs attachment factors have been identified as disruptors of the binding between HuNoVs and HBGAs.•Foods and microorganisms play an important role in the transmission of HuNoVs.•These attachment factors/receptors are pivotal in elucidating the interaction mechanism between HuNoVs and hosts/carriers.
Noroviruses are a leading cause of epidemic and pandemic acute gastroenteritis (AGE) worldwide, and contaminated food and water are important routes for its transmission. Raw sewage has been used for ...viral surveillance to monitor the emergence of new norovirus strains with the potential to cause epidemics. In this study, we investigated norovirus occurrence and norovirus RNA levels in 156 samples collected from May 2013 to May 2014, across three different stages (52 samples each) of a wastewater treatment plant (WWTP) in Rio de Janeiro, Brazil. We also explored norovirus GII diversity in raw sewage samples by next-sequencing generation (NGS). In addition, we examined norovirus prevalence and molecular epidemiology from acute gastroenteritis cases. Using RT-qPCR, norovirus GI and GII was detected in 38.5% and 96.1% of raw sewage samples, 40.4% and 96.1% of primary effluent samples and 1.9% and 5.8% of final effluent samples, respectively. Norovirus RNA levels varied from 4 to 6.2 log10 genome copies per litre (gc L−1) for GI and from 4.4 to 7.3 log10 gc L−1 for GII. Using MiSeq NGS, we identified 13 norovirus genotypes over the one-year period, with six dominant capsid genotypes, including GII.4, GII.17, GII.5, GII.2, GII.3 and GII.1. GII.4 noroviruses were the most prevalent in wastewater samples (68.5%), and a similar trend was observed in AGE cases (71%). The emergent GII.17 was the second most prevalent genotype (14.3%) identified in the raw sewage samples, however, it was not detected in clinical cases. Due to the high burden of norovirus outbreaks and the lack of vaccine and antiviral drugs, it is essential to understand the genotypic diversity of norovirus at the population level. Complementary data obtained from both clinical and environmental (sewage) samples proved to be an effective strategy to monitor the circulation and emergence of norovirus epidemic genotypes.
•We identified 13 norovirus genotypes in the raw sewage using deep sequencing.•Major and minor norovirus GII genotypes were detected from raw sewage.•Norovirus GII.17 genotype was detected prior to its detection in clinical cases.•Secondary sewage treatment decreased norovirus RNA levels to undetected levels.•Autumn/winter seasonality was observed only for norovirus GI.
Silver nanoparticles (AgNP) have strong broad-spectrum antimicrobial activity and gained increased attention for the development of AgNP based products, including medical and food applications. ...Initially, the efficacy of AgNP and silver nitrate (AgNO3) was evaluated for inactivating norovirus surrogates, the feline calicivirus (FCV) and the murine norovirus (MNV). These norovirus surrogates were exposed to AgNO3 and AgNP solutions for 24 h at 25 °C and then analyzed by cell-culture assays. Both AgNP and silver ions significantly decreased FCV and MNV infectivity in a dose-dependent manner between concentrations of 2.1 and 21 mg/L. Furthermore, poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) films were prepared by depositing a coating of thermally post-processed electrospun PHBV18/AgNP fiber mats over compression moulded PHBV3 films. After 24 h exposure at 37 °C and 100% RH, no infectious FCV were recovered when in contact with the AgNP films while MNV titers decreased by 0.86 log. The morphology of the PHBV18 and PHBV18/AgNP fibers studied by SEM showed smooth and continuous fibers in both cases and the EDAX analysis confirmed the homogeneously distribution of AgNP into the coating and onto the PHBV3/PHBV18 layer. This study showed, for the first time, the suitability of the PHBV18/AgNP electrospun coating for antiviral surfaces.
•Antiviral activity of AgNPs and AgNO3 was evaluated on MNV and FCV.•Both significantly decrease FCV and MNV infectivity in a dose-dependent manner.•A PHBV18/AgNPs electrospun coating was produced.•The AgNP electrospun coating completely inactivated FCV based on ISO 22196:2011.
Norovirus is the main cause of viral gastroenteritis worldwide. Although norovirus gastroenteritis is self-limiting in immunocompetent individuals, chronic infections with debilitating and ...life-threatening complications occur in immunocompromised patients. Nitazoxanide (NTZ) has been used empirically in the clinic and has demonstrated effectiveness against norovirus gastroenteritis. In this study, we aimed at uncovering the antiviral potential and mechanisms of action of NTZ and its active metabolite, tizoxanide (TIZ), using a human norovirus (HuNV) replicon. NTZ and TIZ, collectively referred to as thiazolides (TZD), potently inhibited replication of HuNV and a norovirus surrogate, feline calicivirus. Mechanistic studies revealed that TZD activated cellular antiviral response and stimulated the expression of a subset of interferon-stimulated genes (ISGs), particularly interferon regulatory factor 1 (IRF-1), not only in a Huh7 cell-based HuNV replicon, but also in naive Huh7 and Caco-2 cells and novel human intestinal organoids. Overexpression of exogenous IRF-1 inhibited HuNV replication, whereas knockdown of IRF-1 largely attenuated the antiviral activity of TZD, suggesting that IRF-1 mediated TZD inhibition of HuNV. By using a Janus kinase (JAK) inhibitor, CP-690550, and a STAT1 knockout approach, we found that TZD induced antiviral response independently of the classical JAK-signal transducers and activators of transcription (JAK-STAT) pathway. Furthermore, TZD and ribavirin synergized to inhibit HuNV replication and completely depleted the replicons from host cells after long-term treatment. In summary, our results demonstrated that TZD combated HuNV replication through activation of cellular antiviral response, in particular by inducing a prominent antiviral effector, IRF-1. NTZ monotherapy or combination with ribavirin represent promising options for treating norovirus gastroenteritis, especially in immunocompromised patients.
Human noroviruses (HuNoVs) have been found as the leading cause of acute gastroenteritis outbreaks in all age groups and are significantly correlated with the consumption of shellfish. In this study, ...the contamination of HuNoVs in shellfish was estimated through a systematic review and meta-analysis. Studies on the contamination of HuNoVs in shellfish were searched from PubMed, Web of Science, Embase, and Cochrane Library from January 2000 to August 2021. A total of 75 studies were included, and the pooled HuNoVs prevalence in shellfish was 29% (95% CI: 23–35) worldwide. As revealed by the results of the subgroup meta-analysis, the prevalence of dominant genogroup was variable, and 4% (95% CI: 3–6), 13% (95% CI: 10–17), with 7% (95% CI: 4–11) of the samples, respectively, contaminated by GI alone, GII alone, and GI&GII. The HuNoVs prevalence of shellfish in Europe, America, and Asia was 33% (95% CI: 24–43), 24% (95% CI: 7–47), and 27% (95% CI: 18–35), respectively, while only 10% (95% CI: 5–17) in Africa. Furthermore, the prevalence of HuNoVs in shellfish was the highest in spring (35%, 95% CI: 23–49) and winter (35%, 95% CI: 22–50), and the lowest in summer (11%, 95% CI: 5–18). Oysters, clams, and mussels had comparable HuNoVs prevalence of 28% (95% CI: 20–37), 27% (95% CI: 16–39) and 24% (95% CI: 17–32), respectively. The prevalence of HuNoVs in shellfish from harvest areas and markets was 30% (95% CI: 23–38) and 30% (95% CI: 19–41), respectively. The results of this study suggest a substantial burden of HuNoVs in shellfish worldwide, with GII.4 (92.86%) and GII.2 (46.43%) as the predominant genotypes. This study provides information regarding the contamination of HuNoVs in shellfish worldwide, which will contribute to the development of appropriate control measures to prevent shellfish-related HuNoVs gastroenteritis.
•The pooled prevalence of human noroviruses in shellfish was found as 29% (95% CI: 23–35) worldwide.•GII.4 (92.86%, 26/28) was found as the most common genotype in shellfish.•Significant differences were found in the seasonal and geographical prevalence of human noroviruses in shellfish.
Human norovirus (HuNoV) is a non-enveloped, single-stranded, positive-stranded RNA virus belonging to the family Caliciviridae. HuNoVs are important pathogenic microorganisms responsible for causing ...food safety incidents. Numerous species of shellfish are characterized by their abundant nutritional value, excellent healthcare function, and a high economic value. As a filter-feeding animal, shellfish filter the seawater at a rate of 4–20 L per hour and ingest microalgae to meet their physiological needs. Additionally, shellfish are able to continuously accumulate viruses from seawater into their bodies, resulting in a concentration ten or even thousand times higher in their tissues than in the environment. In recent years, more attention has been paid to HuNoV contamination in shellfish in China, and related monitoring studies have been conducted in different areas. However, most of these studies focused on a certain region in a certain period of time, and some species, which are not conducive to a comprehensive understanding of the overall prevalence of HuNoVs in shellfish in China. Meta-analysis refers to the methods which focus on contrasting and combining results from different studies for identifying patterns among the study results or other interesting relationships that may come to light in the context of multiple studies. This study aimed to collect cross-sectional data on the studies conducted on shellfish contamination in China. The search terms used were Norwalk virus, norovirus, shellfish, bivalves, oysters, mussels, clams, cockles, and scallops in all the databases (CNKI, VIP, CBM, WanFang Data, PubMed, Web of Science, Embase, and Cochrane Library). A total of 600 studies on HuNoV contamination of shellfish were initially included in the data. First, 303 duplicate studies were removed, leaving 297 studies remaining. One meta-analysis, 11 reviews, and 16 meeting abstracts were excluded from the first analysis. In the second analysis, abstracts of the remaining 269 studies were read by two independent reviewers, further excluding 221 studies in which experimental designs did not meet the inclusion criteria. After carefully reading the full text of the 48 studies, 11 of them were excluded. Ultimately, 37 studies were included in the final analysis. The total sample size in these 37 studies was 17 162 among which the maximum number of samples in a single study was 2 955, and the minimum was 52, and the total number of HuNoV-contaminated samples was 1 970. The meta-analysis was conducted using Stata 14.0, and the effect size was defined as the prevalence of HuNoVs (percentage). Moreover, the heterogeneity of the studies was examined using Q test (P-value) and I2. The pooled prevalence of HuNoVs in shellfish was found to be 15% with an I2 value of 97.22%, which indicated a strong heterogeneity among the 37 studies. We then grouped them based on genogroups, area, season, and species using a random effect model. As a result, GⅠ and GⅡ were found as the two most prevalent genogroups. As revealed by the results, the prevalence of contamination of GⅠ alone, contamination of GⅡ alone, and the combined contamination of GⅠ and GⅡwas found to be 3%, 10%, and 1%, respectively; both Beijing and Guangdong contributed the most with seven studies, followed by Zhejiang with five studies. In addition, there were four studies conducted each in Jiangsu and Shandong, and Fujian contributed with three studies. Two studies were conducted in Gansu, Guangxi, Hebei, Liaoning, and Shanghai. Only one study has been conducted in Hainan. The geographical location exhibited a significant impact on the prevalence of HuNoVs (P < 0.01), and its prevalence in South China (Guangdong, Guangxi, Hainan), North China (Beijing, Hebei), and East China (Fujian, Jiangsu, Shandong, Shanghai, and Zhejiang) reached 19%, 17%, and 11%, respectively, while those in Northeast China (Liaoning) and Northwest China (Gansu), which were not coastal areas, were 4% and 9%, respectively. HuNoVs contamination in shellfish was found to be significantly correlated with the season. At low temperatures, the virus is more persistent, and shellfish metabolism may be inhibited. Our results showed that the prevalence of HuNoVs was the highest in winter (25%), only 10% in summer, and 16% and 12% in spring and autumn, respectively. HuNoVs may contaminate a wide variety of species during the pre-harvest or post-harvest stages. Oysters, clams, and mussels have been recognized as the most common seafood on the table and therefore these are the most investigated. The results of this meta-analysis revealed that the prevalence of HuNoVs in oysters, mussels, and clams was 16%, 10%, and 9%, respectively. The possible reasons why oysters showed the highest prevalence among all shellfish are as follows. One, the oyster farming area is located in shallow bays, which are easily contaminated by domestic sewage. Second, different oyster tissues contain HuNoV receptors (human histo-blood group antigens (HBGAs)-like carbohydrates) and protein-ligands (oyster heat shock protein 70), which can specifically bind to HuNoVs. In summary, HuNoV contamination in shellfish is common in China, and the region, season, and species exhibit significant effects on the prevalence of HuNoVs. The results of this study are beneficial for gaining insights into the HuNoV contamination in shellfish, demonstrating the importance of continuous HuNoV monitoring. Future studies should establish some effective control measures to ensure the sound growth of the shellfish industry in China.
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