Research

12 pages, 2619 KiB

Open AccessArticle

First Detection and Genomic Characterization of Bovine Norovirus from Yak

by Yuchen Cui, Xi Chen, Hua Yue and Cheng Tang

Pathogens 2022, 11(2), 192; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11020192 - 31 Jan 2022

Cited by 4 | Viewed by 1934

Yak are a unique free-grazing bovine species in high-altitude areas. The objective of this study was to investigate the presence and molecular characteristics of BNoV in yak. A total of 205 diarrheal samples of yak (aged ≤ 3 months) were collected from 10 [...] Read more.

Yak are a unique free-grazing bovine species in high-altitude areas. The objective of this study was to investigate the presence and molecular characteristics of BNoV in yak. A total of 205 diarrheal samples of yak (aged ≤ 3 months) were collected from 10 farms in Sichuan Province, China, from May 2018 to October 2020, and four samples were detected as BNoV-positive with RT-PCR. Moreover, a nearly full-length genome of SMU-YAK-J1 containing three complete ORFs was successfully sequenced. Sequence analysis with only nine genome sequences of the GIII genogroup showed that SMU-YAK-J1 was most closely related with GIII.P2 GIII.4, sharing 90.9% gnomic nucleotide identity, but only shared 71.6–85.9% with other genotypes, which confirmed that SMU-YAK-J1 belongs to genotype GIII.P2 GIII.4. However, compared with the sole genome of GIII.4 in GenBank, the BNoV in this study also exhibited many unique amino acid changes among all the three ORFs, which may represent the unique genetic evolution of BNoV in yak. This study first determined the presence of BNoV in yak, contributing to a better understanding of the prevalence and genetic evolution of BNoV. Full article

(This article belongs to the Special Issue Norovirus and Viral Gastroenteritis)

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15 pages, 976 KiB

Open AccessArticle

Assessment of Food and Waterborne Viral Outbreaks by Using Field Epidemiologic, Modern Laboratory and Statistical Methods—Lessons Learnt from Seven Major Norovirus Outbreaks in Finland

by Aleksandra Polkowska, Sirpa Räsänen, Pekka Nuorti, Leena Maunula and Katri Jalava

Pathogens 2021, 10(12), 1624; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10121624 - 14 Dec 2021

Cited by 1 | Viewed by 2920

Abstract

Seven major food- and waterborne norovirus outbreaks in Western Finland during 2014–2018 were re-analysed. The aim was to assess the effectiveness of outbreak investigation tools and evaluate the Kaplan criteria. We summarised epidemiological and microbiological findings from seven outbreaks. To evaluate the Kaplan [...] Read more.

Seven major food- and waterborne norovirus outbreaks in Western Finland during 2014–2018 were re-analysed. The aim was to assess the effectiveness of outbreak investigation tools and evaluate the Kaplan criteria. We summarised epidemiological and microbiological findings from seven outbreaks. To evaluate the Kaplan criteria, a one-stage meta-analysis of data from seven cohort studies was performed. The case was defined as a person attending an implicated function with diarrhoea, vomiting or two other symptoms. Altogether, 22% (386/1794) of persons met the case definition. Overall adjusted, 73% of norovirus patients were vomiting, the mean incubation period was 44 h (4 h to 4 days) and the median duration of illness was 46 h. As vomiting was a more common symptom in children (96%, 143/149) and diarrhoea among the elderly (92%, 24/26), symptom and age presentation should drive hypothesis formulation. The Kaplan criteria were useful in initial outbreak assessments prior to faecal results. Rapid food control inspections enabled evidence-based, public-health-driven risk assessments. This led to probability-based vehicle identification and aided in resolving the outbreak event mechanism rather than implementing potentially ineffective, large-scale public health actions such as the withdrawal of extensive food lots. Asymptomatic food handlers should be ideally withdrawn from high-risk work for five days instead of the current two days. Food and environmental samples often remain negative with norovirus, highlighting the importance of research collaborations. Electronic questionnaire and open-source novel statistical programmes provided time and resource savings. The public health approach proved useful within the environmental health area with shoe leather field epidemiology, combined with statistical analysis and mathematical reasoning. Full article

(This article belongs to the Special Issue Norovirus and Viral Gastroenteritis)

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19 pages, 3507 KiB

Open AccessArticle

Prevalence and Evolution of Noroviruses between 1966 and 2019, Implications for Vaccine Design

by Hong-Lu Zhou, Li-Na Chen, Song-Mei Wang, Ming Tan, Chao Qiu, Tian-Yi Qiu and Xuan-Yi Wang

Pathogens 2021, 10(8), 1012; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10081012 - 11 Aug 2021

Cited by 7 | Viewed by 2571

Abstract

Noroviruses (NoVs), a group of single-stranded RNA viruses causing epidemic acute gastroenteritis in humans, are highly diverse, consisting of multiple genogroups with >30 genotypes. Their continual evolutions make NoV vaccine design and development difficult. Here, we report a study of NoV sequences obtained [...] Read more.

Noroviruses (NoVs), a group of single-stranded RNA viruses causing epidemic acute gastroenteritis in humans, are highly diverse, consisting of multiple genogroups with >30 genotypes. Their continual evolutions make NoV vaccine design and development difficult. Here, we report a study of NoV sequences obtained from a population-based diarrhea surveillance in Zhengding County of Hebei Province spanning from 2001 to 2019 and those available in the GenBank database from 1966 to 2019. NoV genotypes and/or variants that may evade immunity were screened and identified based on primary and conformational structures for vaccine design. We selected 366, 301, 139, 74 and 495 complete VP1-coding nucleotide sequences representing the predominant genotypes of GII.4, GII.2, GII.3, GII.6 and GII.17, respectively. A total of 16 distinct GII.4 variants were identified, showing a typical linear evolutionary pattern of variant replacement, while only 1–4 variants of the other genotypes were found to co-circulate over the 40–50-year period without typical variant replacement. The vaccine strain GII.4c is close to variant Sydney_2012 (0.053) in their primary structure, but they are distinct at epitopes A and E in conformations. Our data suggested GII.4 variant Sydney_2012, GII.2 variant A, a GII.3 strain, GII.6 variants B and C and GII.17 variant D are primary candidate strains for NoV vaccine development. Full article

(This article belongs to the Special Issue Norovirus and Viral Gastroenteritis)

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8 pages, 382 KiB

Open AccessArticle

Norovirus Persistence in Oysters to Prolonged Commercial Purification

by Roberta Battistini, Chiara Masotti, Valeria Listorti, Elisabetta Suffredini, Cristiana Maurella, Aitor Garcia-Vozmediano, Erica Costa, Francesco Iacona, Mino Orlandi, Carlo Ercolini and Laura Serracca

Pathogens 2021, 10(8), 944; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10080944 - 28 Jul 2021

Cited by 5 | Viewed by 2036

Abstract

Depuration is generally the main treatment employed for bivalve mollusks harvested from contaminated sites. Commercial depuration has demonstrated to be effective for removal of bacterial pathogens, although it probably provides only limited efficacy against human enteric viruses. We evaluated the quantitative reduction of [...] Read more.

Depuration is generally the main treatment employed for bivalve mollusks harvested from contaminated sites. Commercial depuration has demonstrated to be effective for removal of bacterial pathogens, although it probably provides only limited efficacy against human enteric viruses. We evaluated the quantitative reduction of norovirus (NoV) genogroups I and II in naturally contaminated oysters after 1, 4, and 9 days of depuration. The process was conducted in an authorized depuration plant, and NoV concentration was determined by RT-qPCR according to ISO 15216-1:2017 method. Regardless of the NoV genogroup, our results showed no significant reduction in NoV concentration after 1 day of depuration. Higher mean reduction (68%) was obtained after 4 days of treatment, while no further increase was observed after 9 days. Overall, reduction was highly variable, and none of the trials showed statistically significant reduction in NoV RNA concentration at the end of each depuration period. Indeed, NoV concentration remained high in 70% of samples even after 9 days of depuration, with values ranging between 4.0 × 10² and 2.3 × 10⁴ g.c./g. These results indicate that an extension of commercial depuration time does not appear to be effective for reducing or eliminating NoV in oysters. Full article

(This article belongs to the Special Issue Norovirus and Viral Gastroenteritis)

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16 pages, 4852 KiB

Open AccessArticle

Characterization of Functional Components in Bovine Colostrum That Inhibit Norovirus Capsid Protruding Domains Interacting with HBGA Ligands

by Zhaolei Xue, Qi Han, Pengwei Huang, Xi Jiang, Ming Tan, Yaofeng Zhao, Ning Li and Ran Zhang

Pathogens 2021, 10(7), 857; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10070857 - 07 Jul 2021

Cited by 2 | Viewed by 2297

Abstract

Human noroviruses (huNoVs) cause epidemic acute gastroenteritis with significant mortality and morbidity worldwide. However, there are no commercial vaccines or antivirals against these important pathogens so far. In this study, we found that bovine colostrum (bCM) inhibited huNoV VLPs and their capsid-protruding (P) [...] Read more.

Human noroviruses (huNoVs) cause epidemic acute gastroenteritis with significant mortality and morbidity worldwide. However, there are no commercial vaccines or antivirals against these important pathogens so far. In this study, we found that bovine colostrum (bCM) inhibited huNoV VLPs and their capsid-protruding (P) domains binding to histo-blood group antigens (HBGAs) that are huNoV receptor or attachment factors for infection, suggesting that bCM may function as a natural antiviral against huNoVs. We then characterized the bCM for the functional inhibition components by sequentially separating bCM into multiple fractions through various chromatography approaches, followed by determining their inhibitory abilities against huNoV receptor-binding P protein interacting with HBGAs. The protein components of bCM functional fractions were examined by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Our data suggested that some milk proteins, likely in the form of glycoproteins, contribute to the observed blocking effects of bCM. Our findings lay an important foundation to further develop bCM into a potential natural antiviral against huNoVs. Full article

(This article belongs to the Special Issue Norovirus and Viral Gastroenteritis)

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17 pages, 4430 KiB

Open AccessArticle

Simvastatin Reduces Protection and Intestinal T Cell Responses Induced by a Norovirus P Particle Vaccine in Gnotobiotic Pigs

by Jacob Kocher, Tammy Bui Castellucci, Ke Wen, Guohua Li, Xingdong Yang, Shaohua Lei, Xi Jiang and Lijuan Yuan

Pathogens 2021, 10(7), 829; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10070829 - 01 Jul 2021

Viewed by 2134

Abstract

Noroviruses (NoVs) are a leading cause of acute gastroenteritis worldwide. P particles are a potential vaccine candidate against NoV. Simvastatin is a cholesterol-reducing drug that is known to increase NoV infectivity. In this study, we examined simvastatin’s effects on P particle-induced protective efficacy [...] Read more.

Noroviruses (NoVs) are a leading cause of acute gastroenteritis worldwide. P particles are a potential vaccine candidate against NoV. Simvastatin is a cholesterol-reducing drug that is known to increase NoV infectivity. In this study, we examined simvastatin’s effects on P particle-induced protective efficacy and T-cell immunogenicity using the gnotobiotic pig model of human NoV infection and diarrhea. Pigs were intranasally inoculated with three doses (100 µg/dose) of GII.4/VA387-derived P particles together with monophosphoryl lipid A and chitosan adjuvants. Simvastatin-fed pigs received 8 mg/day orally for 11 days prior to challenge. A subset of pigs was orally challenged with 10 ID₅₀ of a NoV GII.4/2006b variant at post-inoculation day (PID) 28 and monitored for 7 days post-challenge. Intestinal and systemic T cell responses were determined pre- and postchallenge. Simvastatin abolished the P particle’s protection and significantly increased diarrhea severity after NoV infection. Simvastatin decreased proliferation of virus-specific and non-specific CD8 T cells in duodenum and virus-specific CD4 and CD8 T cells in spleen and significantly reduced numbers of intestinal mononuclear cells in vaccinated pigs. Furthermore, simvastatin significantly decreased numbers of duodenal CD4+IFN-γ+, CD8+IFN-γ+ and regulatory T cells and total duodenal activated CD4+ and CD8+ T cells in vaccinated pigs pre-challenge at PID 28. Following challenge, simvastatin prevented the IFN-γ+ T cell response in spleen of vaccinated pigs. These results indicate that simvastatin abolished P particle vaccine-induced partial protection through, at least in part, impairing T cell immunity. The findings have specific implications for the development of preventive and therapeutic strategies against NoV gastroenteritis, especially for the elderly population who takes statin-type drugs. Full article

(This article belongs to the Special Issue Norovirus and Viral Gastroenteritis)

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Review

Jump to: Research, Other

15 pages, 1051 KiB

Open AccessReview

Epidemiology, Clinical Features, and Unusual Complications of Norovirus Infection in Taiwan: What We Know after Rotavirus Vaccines

by Meng-Che Lu, Sheng-Chieh Lin, Yi-Hsiang Hsu and Shih-Yen Chen

Pathogens 2022, 11(4), 451; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11040451 - 09 Apr 2022

Cited by 6 | Viewed by 2550

Abstract

Noroviruses (NoVs) are one of the emerging and rapidly spreading groups of pathogens threatening human health. A reduction in sporadic NoV infections was noted following the start of the COVID-19 pandemic, but the return of NoV gastroenteritis during the COVID-19 pandemic has been [...] Read more.

Noroviruses (NoVs) are one of the emerging and rapidly spreading groups of pathogens threatening human health. A reduction in sporadic NoV infections was noted following the start of the COVID-19 pandemic, but the return of NoV gastroenteritis during the COVID-19 pandemic has been noted recently. Research in recent years has shown that different virus strains are associated with different clinical characteristics; moreover, there is a paucity of research into extraintestinal or unusual complications that may be associated with NoV. The genomic diversity of circulating NoVs is also complex and may vary significantly. Therefore, this short narrative review focuses on sharing the Taiwan experience of NoV infection including epidemiology, clinical features, and complications following suboptimal rotavirus immunization in Taiwan (after October 2006). We also highlight the unusual complications associated with NoV infections and the impacts of NoV infection during the COVID-19 pandemic in the literature for possible future research directions. To conclude, further research is needed to quantify the burden of NoV across the spectrum of disease severity in Taiwan. The evidence of the connection between NoV and the unusual complications is still lacking. Full article

(This article belongs to the Special Issue Norovirus and Viral Gastroenteritis)

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8 pages, 223 KiB

Open AccessReview

Norovirus Vaccines: Current Clinical Development and Challenges

by Ming Tan

Pathogens 2021, 10(12), 1641; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10121641 - 19 Dec 2021

Cited by 32 | Viewed by 5358

Abstract

Noroviruses are the major viral pathogens causing epidemic and endemic acute gastroenteritis with significant morbidity and mortality. While vaccines against norovirus diseases have been shown to be of high significance, the development of a broadly effective norovirus vaccine remains difficult, owing to the [...] Read more.

Noroviruses are the major viral pathogens causing epidemic and endemic acute gastroenteritis with significant morbidity and mortality. While vaccines against norovirus diseases have been shown to be of high significance, the development of a broadly effective norovirus vaccine remains difficult, owing to the wide genetic and antigenic diversity of noroviruses with multiple co-circulated variants of various genotypes. In addition, the absence of a robust cell culture system, an efficient animal model, and reliable immune markers of norovirus protection for vaccine evaluation further hinders the developmental process. Among the vaccine candidates that are currently under clinical studies, recombinant VP1-based virus-like particles (VLPs) that mimic major antigenic features of noroviruses are the common ones, with proven safety, immunogenicity, and protective efficacy, supporting a high success likelihood of a useful norovirus vaccine. This short article reviews the recent progress in norovirus vaccine development, focusing on those from recent clinical studies, as well as summarizes the barriers that are being encountered in this developmental process and discusses issues of future perspective. Full article

(This article belongs to the Special Issue Norovirus and Viral Gastroenteritis)

Other

Jump to: Research, Review

17 pages, 1008 KiB

Open AccessPerspective

Illuminating Human Norovirus: A Perspective on Disinfection of Water and Surfaces Using UVC, Norovirus Model Organisms, and Radiation Safety Considerations

by Richard M. Mariita, James H. Davis and Rajul V. Randive

Pathogens 2022, 11(2), 226; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11020226 - 08 Feb 2022

Cited by 3 | Viewed by 4486

Abstract

Human noroviruses (HuNoVs) are a major cause of gastroenteritis and are associated with high morbidity because of their ability to survive in the environment and small inoculum size required for infection. Norovirus is transmitted through water, food, high touch-surfaces, and human-to-human contact. Ultraviolet [...] Read more.

Human noroviruses (HuNoVs) are a major cause of gastroenteritis and are associated with high morbidity because of their ability to survive in the environment and small inoculum size required for infection. Norovirus is transmitted through water, food, high touch-surfaces, and human-to-human contact. Ultraviolet Subtype C (UVC) light-emitting diodes (LEDs) can disrupt the norovirus transmission chain for water, food, and surfaces. Here, we illuminate considerations to be adhered to when picking norovirus surrogates for disinfection studies and shine light on effective use of UVC for norovirus infection control in water and air and validation for such systems and explore the blind spot of radiation safety considerations when using UVC disinfection strategies. This perspective also discusses the promise of UVC for norovirus mitigation to save and ease life. Full article

(This article belongs to the Special Issue Norovirus and Viral Gastroenteritis)

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