Research

12 pages, 1939 KiB

Open AccessArticle

Glucose Reduces Norovirus Binding to Enterobacter cloacae and Alters Gene Expression of Bacterial Surface Structures in a Growth Phase Dependent Manner

by Kendall J. Long, Chanel A. Mosby and Melissa K. Jones

Viruses 2022, 14(8), 1596; https://doi.org/10.3390/v14081596 - 22 Jul 2022

Cited by 1 | Viewed by 1563

Abstract

Norovirus is the leading cause of acute viral gastroenteritis. Both human and murine noroviruses attach to commensal bacteria belonging to the mammalian gut flora, and binding levels are influenced by nutrients present in bacterial media. However, it is not known which nutrients are [...] Read more.

Norovirus is the leading cause of acute viral gastroenteritis. Both human and murine noroviruses attach to commensal bacteria belonging to the mammalian gut flora, and binding levels are influenced by nutrients present in bacterial media. However, it is not known which nutrients are responsible for altering viral binding or why binding is altered. Gene expression of commensal bacteria can be changed by the external environment as well as by interaction with pathogens. For example, growth phase and incubation conditions impact expression levels of specific bacterial genes in Escherichia coli. We have previously shown that binding by both human and murine noroviruses to the commensal bacterium Enterobacter cloacae induces genome-wide changes in gene expression with a large number of differentially expressed genes associated with the surface structure of the bacterial cell. The current study evaluated norovirus binding under nutrient-limited conditions and assessed the expression of a select panel of these genes that are significantly altered by norovirus binding under these conditions. The goal of this work was to determine how norovirus attachment to Enterobacter cloacae affected the expression of these genes under varying nutrient and growth phase conditions. We found that the presence of glucose in minimal media reduced murine norovirus binding to E. cloacae and viral binding in the presence of glucose reduced gene expression for surface structures previously associated with norovirus attachment. Changes in viral binding and gene expression occurred in a growth phase-dependent manner. Collectively, these data demonstrate that both the growth phase and nutrient availability alter viral interactions with commensal bacteria and the subsequent changes in gene expression. Ultimately, this work advances our understanding of norovirus-bacterium interactions and provides a foundation for elucidating the conditions and surface structures that regulate norovirus attachment to bacteria. Full article

(This article belongs to the Special Issue Noroviruses 2021)

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9 pages, 1634 KiB

Open AccessArticle

Norovirus Genogroup II Epidemics and the Potential Effect of Climate Change on Norovirus Transmission in Taiwan

by Shu-Chun Chiu, Szu-Chieh Hu, Ling-Min Liao, Yu-Hua Chen and Jih-Hui Lin

Viruses 2022, 14(3), 641; https://doi.org/10.3390/v14030641 - 20 Mar 2022

Viewed by 2408

Abstract

The activity of norovirus varies from season to season, and the effect of climate change on the incidence of norovirus outbreaks is a widely recognized yet poorly understood phenomenon. Investigation of the possible association between climatic factors and the incidence of norovirus is [...] Read more.

The activity of norovirus varies from season to season, and the effect of climate change on the incidence of norovirus outbreaks is a widely recognized yet poorly understood phenomenon. Investigation of the possible association between climatic factors and the incidence of norovirus is key to a better understanding of the epidemiology of norovirus and early prediction of norovirus outbreaks. In this study, clinical stool samples from acute gastroenteritis outbreaks were collected from January 2015 to June 2019 in Taiwan. Data analysis from our study indicated that more than half of the cases were reported in the winter and spring seasons, including those caused by norovirus of genotypes GII (genogroup II).2, GII.3, GII.6, and GII.17, and 45.1% of the patients who tested positive for norovirus were infected by the GII.4 norovirus in autumn. However, GII.6 norovirus accounted for a higher proportion of the cases reported in summer than any other strain. Temperature is a crucial factor influencing patterns of epidemic outbreaks caused by distinct genotypes of norovirus. The results of this study may help experts predict and issue early public warnings of norovirus transmission and understand the effect of climate change on norovirus outbreaks caused by different genotypes and occurring in different locations. Full article

(This article belongs to the Special Issue Noroviruses 2021)

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16 pages, 1655 KiB

Open AccessArticle

Epidemiological and Genetic Characterization of Norovirus Outbreaks That Occurred in Catalonia, Spain, 2017–2019

by Eduard Anfruns-Estrada, Sara Sabaté, Efrén Razquin, Thais Cornejo Sánchez, Rosa Bartolomé, Nuria Torner, Conchita Izquierdo, Nuria Soldevila, Lorena Coronas, Àngela Domínguez, Cristina Fuentes, Rosa M. Pintó, Albert Bosch, Susana Guix and The Working Group for the Study of Outbreaks of Acute Gastroenteritis in Catalonia (PI16/02005)

Viruses 2022, 14(3), 488; https://doi.org/10.3390/v14030488 - 27 Feb 2022

Cited by 8 | Viewed by 1920

Abstract

Molecular characterization of human norovirus (HuNoV) genotypes enhances the understanding of viral features and illustrates distinctive evolutionary patterns. The aim of our study was to describe the prevalence of the genetic diversity and the epidemiology of the genotypes involved in HuNoV outbreaks in [...] Read more.

Molecular characterization of human norovirus (HuNoV) genotypes enhances the understanding of viral features and illustrates distinctive evolutionary patterns. The aim of our study was to describe the prevalence of the genetic diversity and the epidemiology of the genotypes involved in HuNoV outbreaks in Catalonia (Spain) between 2017 and 2019. A total of 100 HuNoV outbreaks were notified with the predominance of GII (70%), followed by GI (27%) and mixed GI/GII (3%). Seasonality was observed for GII outbreaks only. The most prevalent genotypes identified were GII.4[P31] Sydney 2012, GII.4[P16] Sydney 2012 and GII.2[P16]. As compared to person-to-person (P/P) transmitted outbreaks, foodborne outbreaks showed significantly higher attack rates and lower duration. The average attack rate was higher in youth hostel/campgrounds compared to nursing homes. Only genotypes GI.4[P4], GII.2[P16], GII.4[P16], GII.4[P31] and GII.17[P17] were consistently detected every year, and only abundance of GII.2[P16] showed a negative trend over time. GII.4 Sydney 2012 outbreaks were significantly associated to nursing homes, while GII.2[P16] and GI.3[P3] were most frequently identified in youth hostel/campgrounds. The average attack rate was significantly higher when comparing GII.2[P16] vs. GI.4[P4], GII.2[P16] vs. GII.4[P31] Sydney 2012, and GII.6[P7] vs. GII.4[P31] Sydney 2012. No correlations were found between genotype and outbreak duration or age of affected individuals. Full article

(This article belongs to the Special Issue Noroviruses 2021)

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16 pages, 3068 KiB

Open AccessArticle

A Novel Class of Norovirus Inhibitors Targeting the Viral Protease with Potent Antiviral Activity In Vitro and In Vivo

by Jana Van Dycke, Wenhao Dai, Zoe Stylianidou, Jian Li, Arno Cuvry, Emma Roux, Bingqian Li, Jasper Rymenants, Lindsey Bervoets, Peter de Witte, Hong Liu, Johan Neyts and Joana Rocha-Pereira

Viruses 2021, 13(9), 1852; https://doi.org/10.3390/v13091852 - 16 Sep 2021

Cited by 8 | Viewed by 3002

Abstract

Human noroviruses (HuNoVs) are the most common cause of viral gastroenteritis resulting annually in ~219,000 deaths and a societal cost of ~USD 60 billion, and no antivirals or vaccines are available. Here, we assess the anti-norovirus activity of new peptidomimetic aldehydes related to [...] Read more.

Human noroviruses (HuNoVs) are the most common cause of viral gastroenteritis resulting annually in ~219,000 deaths and a societal cost of ~USD 60 billion, and no antivirals or vaccines are available. Here, we assess the anti-norovirus activity of new peptidomimetic aldehydes related to the protease inhibitor rupintrivir. The early hit compound 4 inhibited the replication of murine norovirus (MNV) and the HuNoV GI.1 replicon in vitro (EC₅₀ ~1 µM) and swiftly cleared the HuNoV GI.1 replicon from the cells. Compound 4 still inhibits the proteolytic activity. We selected a resistant GI.1 replicon, with a mutation (I109V) in a highly conserved region of the viral protease, conferring a low yield of resistance against compound 4 and rupintrivir. After testing new derivatives, compound 10d was the most potent (EC₅₀ nanomolar range). Molecular docking indicated that the aldehyde group of compounds 4 and 10d bind with Cys139 in the HuNoV 3CL protease by a covalent linkage. Finally, compound 10d inhibited the replication of HuNoV GII.4 in infected zebrafish larvae, and PK studies in mice showed an adequate profile. Full article

(This article belongs to the Special Issue Noroviruses 2021)

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16 pages, 2161 KiB

Open AccessArticle

Virological and Epidemiological Features of Norovirus Infections in Brazil, 2017–2018

by Sylvia Kahwage Sarmento, Juliana da Silva Ribeiro de Andrade, Marize Pereira Miagostovich and Tulio Machado Fumian

Viruses 2021, 13(9), 1724; https://doi.org/10.3390/v13091724 - 30 Aug 2021

Cited by 7 | Viewed by 2641

Abstract

Noroviruses are considered an important cause of acute gastroenteritis (AGE) across all age groups. Here, we investigated the incidence of norovirus, genotypes circulation, and norovirus shedding in AGE stool samples from outpatients in Brazil. During a two-year period, 1546 AGE stool samples from [...] Read more.

Noroviruses are considered an important cause of acute gastroenteritis (AGE) across all age groups. Here, we investigated the incidence of norovirus, genotypes circulation, and norovirus shedding in AGE stool samples from outpatients in Brazil. During a two-year period, 1546 AGE stool samples from ten Brazilian states were analyzed by RT-qPCR to detect and quantify GI and GII noroviruses. Positive samples were genotyped by dual sequencing using the ORF1/2 junction region. Overall, we detected norovirus in 32.1% of samples, with a massive predominance of GII viruses (89.1%). We also observed a significant difference between the median viral load of norovirus GI (3.4×10⁵ GC/g of stool) and GII (1.9×10⁷ GC/g). The most affected age group was children aged between 6 and 24 m old, and norovirus infection was detected throughout the year without marked seasonality. Phylogenetic analysis of partial RdRp and VP1 regions identified six and 11 genotype combinations of GI and GII, respectively. GII.4 Sydney[P16] was by far the predominant genotype (47.6%), followed by GII.2[P16], GII.4 Sydney[P31], and GII.6[P7]. We detected, for the first time in Brazil, the intergenogroup recombinant genotype GIX.1[GII.P15]. Our study contributes to the knowledge of norovirus genotypes circulation at the national level, reinforcing the importance of molecular surveillance programs for future vaccine designs. Full article

(This article belongs to the Special Issue Noroviruses 2021)

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11 pages, 1199 KiB

Open AccessCommunication

Analysis of Synchronous and Asynchronous In Vitro Infections with Homologous Murine Norovirus Strains Reveals Time-Dependent Viral Interference Effects

by Louisa F. Ludwig-Begall, Elisabetta Di Felice, Barbara Toffoli, Chiara Ceci, Barbara Di Martino, Fulvio Marsilio, Axel Mauroy and Etienne Thiry

Viruses 2021, 13(5), 823; https://doi.org/10.3390/v13050823 - 02 May 2021

Cited by 1 | Viewed by 1861

Abstract

Viral recombination is a key mechanism in the evolution and diversity of noroviruses. In vivo, synchronous single-cell coinfection by multiple viruses, the ultimate prerequisite to viral recombination, is likely to be a rare event and delayed secondary infections are a more probable occurrence. [...] Read more.

Viral recombination is a key mechanism in the evolution and diversity of noroviruses. In vivo, synchronous single-cell coinfection by multiple viruses, the ultimate prerequisite to viral recombination, is likely to be a rare event and delayed secondary infections are a more probable occurrence. Here, we determine the effect of a temporal separation of in vitro infections with the two homologous murine norovirus strains MNV-1 WU20 and CW1 on the composition of nascent viral populations. WU20 and CW1 were either synchronously inoculated onto murine macrophage cell monolayers (coinfection) or asynchronously applied (superinfection with varying titres of CW1 at half-hour to 24-h delays). Then, 24 h after initial co-or superinfection, quantification of genomic copy numbers and discriminative screening of plaque picked infectious progeny viruses demonstrated a time-dependent predominance of primary infecting WU20 in the majority of viral progenies. Our results indicate that a time interval from one to two hours onwards between two consecutive norovirus infections allows for the establishment of a barrier that reduces or prevents superinfection. Full article

(This article belongs to the Special Issue Noroviruses 2021)

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Review

Jump to: Research, Other

17 pages, 2368 KiB

Open AccessReview

Swine Norovirus: Past, Present, and Future

by Lara Cavicchio, Andrea Laconi, Alessandra Piccirillo and Maria Serena Beato

Viruses 2022, 14(3), 537; https://doi.org/10.3390/v14030537 - 05 Mar 2022

Cited by 5 | Viewed by 2777

Abstract

Norovirus, an ssRNA + virus of the family Caliciviridae, is a leading disease burden in humans worldwide, causing an estimated 600 million cases of acute gastroenteritis every year. Since the discovery of norovirus in the faeces of swine in Japan in the [...] Read more.

Norovirus, an ssRNA + virus of the family Caliciviridae, is a leading disease burden in humans worldwide, causing an estimated 600 million cases of acute gastroenteritis every year. Since the discovery of norovirus in the faeces of swine in Japan in the 1990s, swine norovirus has been reported in several countries on several continents. The identification of the human-associated GII.4 genotype in swine has raised questions about this animal species as a reservoir of norovirus with zoonotic potential, even if species-specific P-types are usually detected in swine. This review summarises the available data regarding the geographic distribution of norovirus in swine, the years of detection, the genotype characterisation, and the prevalence in specific production groups. Furthermore, we discuss the major bottlenecks for the detection and characterisation of swine noroviruses. Full article

(This article belongs to the Special Issue Noroviruses 2021)

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18 pages, 601 KiB

Open AccessReview

Norovirus: Facts and Reflections from Past, Present, and Future

by Yalda Lucero, David O. Matson, Shai Ashkenazi, Sergio George and Miguel O’Ryan

Viruses 2021, 13(12), 2399; https://doi.org/10.3390/v13122399 - 30 Nov 2021

Cited by 19 | Viewed by 5852

Abstract

Human Norovirus is currently the main viral cause of acute gastroenteritis (AGEs) in most countries worldwide. Nearly 50 years after the discovery of the “Norwalk virus” by Kapikian and colleagues, the scientific and medical community continue to generate new knowledge on the full [...] Read more.

Human Norovirus is currently the main viral cause of acute gastroenteritis (AGEs) in most countries worldwide. Nearly 50 years after the discovery of the “Norwalk virus” by Kapikian and colleagues, the scientific and medical community continue to generate new knowledge on the full biological and disease spectrum of Norovirus infection. Nevertheless, several areas remain incompletely understood due to the serious constraints to effectively replicate and propagate the virus. Here, we present a narrated historic perspective and summarize our current knowledge, including insights and reflections on current points of interest for a broad medical community, including clinical and molecular epidemiology, viral–host–microbiota interactions, antivirals, and vaccine prototypes. We also include a reflection on the present and future impacts of the COVID-19 pandemic on Norovirus infection and disease. Full article

(This article belongs to the Special Issue Noroviruses 2021)

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36 pages, 2168 KiB

Open AccessReview

Noroviruses—The State of the Art, Nearly Fifty Years after Their Initial Discovery

by Louisa F. Ludwig-Begall, Axel Mauroy and Etienne Thiry

Viruses 2021, 13(8), 1541; https://doi.org/10.3390/v13081541 - 04 Aug 2021

Cited by 37 | Viewed by 7341

Abstract

Human noroviruses are recognised as the major global cause of viral gastroenteritis. Here, we provide an overview of notable advances in norovirus research and provide a short recap of the novel model systems to which much of the recent progress is owed. Significant [...] Read more.

Human noroviruses are recognised as the major global cause of viral gastroenteritis. Here, we provide an overview of notable advances in norovirus research and provide a short recap of the novel model systems to which much of the recent progress is owed. Significant advances include an updated classification system, the description of alternative virus-like protein morphologies and capsid dynamics, and the further elucidation of the functions and roles of various viral proteins. Important milestones include new insights into cell tropism, host and microbial attachment factors and receptors, interactions with the cellular translational apparatus, and viral egress from cells. Noroviruses have been detected in previously unrecognised hosts and detection itself is facilitated by improved analytical techniques. New potential transmission routes and/or viral reservoirs have been proposed. Recent in vivo and in vitro findings have added to the understanding of host immunity in response to norovirus infection, and vaccine development has progressed to preclinical and even clinical trial testing. Ongoing development of therapeutics includes promising direct-acting small molecules and host-factor drugs. Full article

(This article belongs to the Special Issue Noroviruses 2021)

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Other

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9 pages, 1925 KiB

Open AccessBrief Report

Aetiological Characteristics of Infectious Diarrhea in Yantai City, Shandong Province, China in 2017

by Zhenlu Sun, Jinjie Xu, Peihua Niu, Miao Jin, Qiao Gao, Ruiqing Zhang, Ji Wang, Yong Zhang and Xuejun Ma

Viruses 2022, 14(2), 216; https://doi.org/10.3390/v14020216 - 23 Jan 2022

Cited by 3 | Viewed by 2594

Abstract

This study aimed to analyse the pathogenic spectrum and epidemiological characteristics of infectious diarrhea in Yantai City, Shandong Province, China and provide a reference for its prevention and control. A total of 713 stool specimens collected within 3 days of diarrhea onset from [...] Read more.

This study aimed to analyse the pathogenic spectrum and epidemiological characteristics of infectious diarrhea in Yantai City, Shandong Province, China and provide a reference for its prevention and control. A total of 713 stool specimens collected within 3 days of diarrhea onset from January to December 2017 at secondary or higher hospitals in Yantai City were tested for 10 causative pathogens, using real-time polymerase chain reaction (RT-PCR). The top two rotaviruses and norovirus were analysed for typing and geographical distribution. The total positive rate was 46.56% (332/713), and 268 of 713 specimens contained at least one pathogen; 64 had at least two pathogens, accounting for 19.28% of the positive specimens (64/332). The positivity rates of rotavirus (RV), norovirus (NoVs) GI, norovirus (NoVs) GII, enterovirus universal (EV), enteric adenoviruses (EAdV), sapovirus (SaV), astrovirus (Astv), Salmonella (SE), Listeria monocytogenes (LiMo), and Vibrio parahaemolyticus (VP) were 20.06% (143/713), 1.82% (13/713), 12.84% (89/713), 10.66% (76/713), 4.07% (29/713), 0.42% (3/713), 2.38% (17/713), 1.54% (11/713), 1.82% (13/713), and 1.54% (11/713), respectively. Infectious diarrhea showed a high prevalence in young children aged 1-5 years, accounting for 48.6% of the total number of cases. Bacterial diarrhea was predominant in summer, and viral diarrhea was distributed throughout the year, without a significant seasonal pattern. Rotavirus is dominated by G9P, accounting for 81.82%, while norovirus is dominated by the GII type and has diverse characteristics. The aetiology of infectious diarrhea in Yantai is mainly viral, with RV, NoVs, EV, EAdV, and Astv being the most frequent pathogens. Continuous surveillance of infectious diarrhea diseases can help us understand its epidemiological and pathogenic characteristics, thereby taking targeted preventive and control measures in different seasons. Full article

(This article belongs to the Special Issue Noroviruses 2021)

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13 pages, 415 KiB

Open AccessBrief Report

Generation of Nucleic Acid Aptamer Candidates against a Novel Calicivirus Protein Target

by Jeremy Faircloth, Matthew D. Moore, Sloane Stoufer, Minji Kim and Lee-Ann Jaykus

Viruses 2021, 13(9), 1716; https://doi.org/10.3390/v13091716 - 29 Aug 2021

Cited by 4 | Viewed by 1762

Abstract

Human norovirus is the leading cause of foodborne illness globally. One of the challenges in detecting noroviruses is the identification of a completely broadly reactive ligand; however, all detection ligands generated to date target the viral capsid, the outermost of which is the [...] Read more.

Human norovirus is the leading cause of foodborne illness globally. One of the challenges in detecting noroviruses is the identification of a completely broadly reactive ligand; however, all detection ligands generated to date target the viral capsid, the outermost of which is the most variable region of the genome. The VPg is a protein covalently linked to the viral genome that is necessary for replication but hitherto remains underexplored as a target for detection or therapeutics. The purpose of this work was to generate nucleic acid aptamers against human norovirus (Norwalk) and cultivable surrogate (Tulane) VPgs for future use in detection and therapeutics. Eight rounds of positive-SELEX and two rounds of counter-SELEX were performed. Five and eight unique aptamer sequences were identified for Norwalk and Tulane VPg, respectively, all of which were predicted to be stable (∆G < −5.0) and one of which occurred in both pools. All candidates displayed binding to both Tulane and Norwalk VPg (positive:negative > 5.0), and all but two of the candidates displayed very strong binding (positive:negative > 10.0), significantly higher than binding to the negative control protein (p < 0.05). Overall, this work reports a number of aptamer candidates found to be broadly reactive and specific for in vitro-expressed VPgs across genus that could be used for future application in detection or therapeutics. Future work characterizing binding of the aptamer candidates against native VPgs and in therapeutic applications is needed to further evaluate their application. Full article

(This article belongs to the Special Issue Noroviruses 2021)

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