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Viruses
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Human Norovirus
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Human Norovirus

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 12795

Special Issue Editors

Dr. Xiaoli Pang

E-Mail Website
Guest Editor
1. Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
2. Public Health Laboratories (ProvLab), Alberta Precision Laboratories (APL), Edmonton, AB, Canada
Interests: enteric viruses; norovirus genetic evolution; clinical diagnosis; molecular epidemiology; environmental virology
Dr. Bonita Lee

E-Mail Website
Guest Editor
Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
Interests: infectious disease and molecular epidemiology; gastroenteritis virus; respiratory virus; C. difficile; infection prevention control

Special Issue Information

Dear Colleague,

Human norovirus (HuNoV) causes approximately 18% of all gastroenteritis cases in all ages and is recognized as the leading cause of gastroenteritis outbreaks around the world.  While the prevalence of HuNoV disease seems to be similar across the continents, an overwhelming majority of HuNoV-associated deaths occur in WHO-defined developing countries.  HuNoV disease also has a significant economic impact, with an estimated global economic burden of USD 60.3 billion dollars per year, including health care costs and productivity loses.  Costs due to productivity losses in high-income countries are particularly high.

Concerted efforts to control HuNoV disease face major challenges, including: the genetic diversity of virus and ongoing evolution, strain-restrictive culture systems with low efficiency, and the limited knowledge of host factors that play a role in HuNoV infection, and protective immunity against HuNoV. The periodical emergence of novel HuNoV strains leading to global pandemics is also a major concern. The vast genetic diversity of HuNoV imposes a hurdle for the development of a vaccine that can provide broad coverage across all strains.  Global HuNoV surveillance is necessary even after the introduction of vaccines to monitor vaccine effectiveness.  In vitro human norovirus culture is an invaluable tool that requires further optimization to support multiple passages, increase permissiveness to more strains, and achieve high virus titers.  The current HIE culture system represents a fairly realistic model that allows researchers to study host factors beyond HBGAs, HuNoV entry and infection, and neutralizing antibody responses.

For this Special Issue, we are inviting the submission of papers focusing on both fundamental and applied aspects of norovirus research. Review papers and original research papers are welcome.

Dr. Xiaoli Pang
Dr. Bonita Lee
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • virus replication and tropism
  • development of cost effective, point-of-care diagnostic assays
  • genetic evolution
  • pathogenesis
  • disinfection
  • antivirals and vaccines
  • foodborne and waterborne norovirus

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Related Special Issue

Published Papers (5 papers)

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Research

21 pages, 4483 KiB  
Article
Molecular Evolutionary Analyses of the RNA-Dependent RNA Polymerase (RdRp) Region and VP1 Gene in Human Norovirus Genotypes GII.P6-GII.6 and GII.P7-GII.6
by Tomoko Takahashi, Ryusuke Kimura, Tatsuya Shirai, Mitsuru Sada, Toshiyuki Sugai, Kosuke Murakami, Kazuhiko Harada, Kazuto Ito, Yuki Matsushima, Fuminori Mizukoshi, Kaori Okayama, Yuriko Hayashi, Mayumi Kondo, Tsutomu Kageyama, Yoshiyuki Suzuki, Haruyuki Ishii, Akihide Ryo, Kazuhiko Katayama, Kiyotaka Fujita and Hirokazu Kimura
Viruses 2023, 15(7), 1497; https://doi.org/10.3390/v15071497 - 1 Jul 2023
Cited by 3 | Viewed by 1896
Abstract
To understand the evolution of GII.P6-GII.6 and GII.P7-GII.6 strains, the prevalent human norovirus genotypes, we analysed both the RdRp region and VP1 gene in globally collected strains using authentic bioinformatics technologies. A common ancestor of the P6- and P7-type RdRp region emerged approximately [...] Read more.
To understand the evolution of GII.P6-GII.6 and GII.P7-GII.6 strains, the prevalent human norovirus genotypes, we analysed both the RdRp region and VP1 gene in globally collected strains using authentic bioinformatics technologies. A common ancestor of the P6- and P7-type RdRp region emerged approximately 50 years ago and a common ancestor of the P6- and P7-type VP1 gene emerged approximately 110 years ago. Subsequently, the RdRp region and VP1 gene evolved. Moreover, the evolutionary rates were significantly faster for the P6-type RdRp region and VP1 gene than for the P7-type RdRp region and VP1 genes. Large genetic divergence was observed in the P7-type RdRp region and VP1 gene compared with the P6-type RdRp region and VP1 gene. The phylodynamics of the RdRp region and VP1 gene fluctuated after the year 2000. Positive selection sites in VP1 proteins were located in the antigenicity-related protruding 2 domain, and these sites overlapped with conformational epitopes. These results suggest that the GII.6 VP1 gene and VP1 proteins evolved uniquely due to recombination between the P6- and P7-type RdRp regions in the HuNoV GII.P6-GII.6 and GII.P7-GII.6 virus strains. Full article
(This article belongs to the Special Issue Human Norovirus)
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15 pages, 6044 KiB  
Article
Identification of Potential Proteinaceous Ligands of GI.1 Norovirus in Pacific Oyster Tissues
by Chenang Lyu, Jingwen Li, Zhentao Shi, Ran An, Yanfei Wang, Guangda Luo and Dapeng Wang
Viruses 2023, 15(3), 631; https://doi.org/10.3390/v15030631 - 25 Feb 2023
Cited by 3 | Viewed by 1832
Abstract
Human norovirus (HuNoV) is the leading foodborne pathogen causing nonbacterial gastroenteritis worldwide. The oyster is an important vehicle for HuNoV transmission, especially the GI.1 HuNoV. In our previous study, oyster heat shock protein 70 (oHSP 70) was identified as the first proteinaceous ligand [...] Read more.
Human norovirus (HuNoV) is the leading foodborne pathogen causing nonbacterial gastroenteritis worldwide. The oyster is an important vehicle for HuNoV transmission, especially the GI.1 HuNoV. In our previous study, oyster heat shock protein 70 (oHSP 70) was identified as the first proteinaceous ligand of GII.4 HuNoV in Pacific oysters besides the commonly accepted carbohydrate ligands, a histo-blood group antigens (HBGAs)-like substance. However the mismatch of the distribution pattern between discovered ligands and GI.1 HuNoV suggests that other ligands may exist. In our study, proteinaceous ligands for the specific binding of GI.1 HuNoV were mined from oyster tissues using a bacterial cell surface display system. Fifty-five candidate ligands were identified and selected through mass spectrometry identification and bioinformatics analysis. Among them, the oyster tumor necrosis factor (oTNF) and oyster intraflagellar transport protein (oIFT) showed strong binding abilities with the P protein of GI.1 HuNoV. In addition, the highest mRNA level of these two proteins was found in the digestive glands, which is consistent with GI.1 HuNoV distribution. Overall the findings suggested that oTNF and oIFT may play important roles in the bioaccumulation of GI.1 HuNoV. Full article
(This article belongs to the Special Issue Human Norovirus)
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16 pages, 1583 KiB  
Article
Norovirus Infection in Young Nicaraguan Children Induces Durable and Genotype-Specific Antibody Immunity
by Paul D. Brewer-Jensen, Yaoska Reyes, Sylvia Becker-Dreps, Fredman González, Michael L. Mallory, Lester Gutiérrez, Omar Zepeda, Edwing Centeno, Nadja Vielot, Marta Diez-Valcarce, Jan Vinjé, Ralph Baric, Lisa C. Lindesmith and Filemon Bucardo
Viruses 2022, 14(9), 2053; https://doi.org/10.3390/v14092053 - 16 Sep 2022
Cited by 5 | Viewed by 2607
Abstract
There are significant challenges to the development of a pediatric norovirus vaccine, mainly due to the antigenic diversity among strains infecting young children. Characterizing human norovirus serotypes and understanding norovirus immunity in naïve children would provide key information for designing rational vaccine platforms. [...] Read more.
There are significant challenges to the development of a pediatric norovirus vaccine, mainly due to the antigenic diversity among strains infecting young children. Characterizing human norovirus serotypes and understanding norovirus immunity in naïve children would provide key information for designing rational vaccine platforms. In this study, 26 Nicaraguan children experiencing their first norovirus acute gastroenteritis (AGE) episode during the first 18 months of life were investigated. We used a surrogate neutralization assay that measured antibodies blocking the binding of 13 different norovirus virus-like particles (VLPs) to histo-blood group antigens (HBGAs) in pre- and post-infection sera. To assess for asymptomatic norovirus infections, stools from asymptomatic children were collected monthly, screened for norovirus by RT-qPCR and genotyped by sequencing. Seroconversion of an HBGA-blocking antibody matched the infecting genotype in 25 (96%) of the 26 children. A subset of 13 (50%) and 4 (15%) of the 26 children experienced monotypic GII and GI seroconversion, respectively, strongly suggesting a type-specific response in naïve children, and 9 (35%) showed multitypic seroconversion. The most frequent pairing in multitypic seroconversion (8/12) were GII.4 Sydney and GII.12 noroviruses, both co-circulating at the time. Blocking antibody titers to these two genotypes did not correlate with each other, suggesting multiple exposure rather than cross-reactivity between genotypes. In addition, GII titers remained consistent for at least 19 months post-infection, demonstrating durable immunity. In conclusion, the first natural norovirus gastroenteritis episodes in these young children were dominated by a limited number of genotypes and induced responses of antibodies blocking binding of norovirus VLPs in a genotype-specific manner, suggesting that an effective pediatric norovirus vaccine likely needs to be multivalent and include globally dominant genotypes. The duration of protection from natural infections provides optimism for pediatric norovirus vaccines administered early in life. Full article
(This article belongs to the Special Issue Human Norovirus)
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13 pages, 2026 KiB  
Article
Antigenic Site Immunodominance Redirection Following Repeat Variant Exposure
by Lisa C. Lindesmith, Paul D. Brewer-Jensen, Michael L. Mallory, Mark R. Zweigart, Samantha R. May, Daniel Kelly, Rachel Williams, Sylvia Becker-Dreps, Filemón Bucardo, David J. Allen, Judith Breuer and Ralph S. Baric
Viruses 2022, 14(6), 1293; https://doi.org/10.3390/v14061293 - 14 Jun 2022
Cited by 5 | Viewed by 2369
Abstract
Human norovirus is a leading cause of acute gastroenteritis, driven by antigenic variants within the GII.4 genotype. Antibody responses to GII.4 vaccination in adults are shaped by immune memory. How children without extensive immune memory will respond to GII.4 vaccination has not been [...] Read more.
Human norovirus is a leading cause of acute gastroenteritis, driven by antigenic variants within the GII.4 genotype. Antibody responses to GII.4 vaccination in adults are shaped by immune memory. How children without extensive immune memory will respond to GII.4 vaccination has not been reported. Here, we characterized the GII.4 neutralizing antibody (nAb) landscape following natural infection using a surrogate assay and antigenic site chimera virus-like particles. We demonstrate that the nAb landscape changes with age and virus exposure. Among sites A, C, and G, nAbs from first infections are focused on sites A and C. As immunity develops with age/exposure, site A is supplemented with antibodies that bridge site A to sites C and G. Cross-site nAbs continue to develop into adulthood, accompanied by an increase in nAb to site G. Continued exposure to GII.4 2012 Sydney correlated with a shift to co-dominance of sites A and G. Furthermore, site G nAbs correlated with the broadening of nAb titer across antigenically divergent variants. These data describe fundamental steps in the development of immunity to GII.4 over a lifetime, and illustrate how the antigenicity of one pandemic variant could influence the pandemic potential of another variant through the redirection of immunodominant epitopes. Full article
(This article belongs to the Special Issue Human Norovirus)
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18 pages, 2517 KiB  
Article
Human Norovirus Induces Aquaporin 1 Production by Activating NF-κB Signaling Pathway
by Mudan Zhang, Binman Zhang, Rui Chen, Miaomiao Li, Zifeng Zheng, Wanfu Xu, Yifan Zhang, Sitang Gong and Qinxue Hu
Viruses 2022, 14(4), 842; https://doi.org/10.3390/v14040842 - 18 Apr 2022
Cited by 5 | Viewed by 3008
Abstract
Human norovirus (HuNoV) is one of the major pathogens of acute nonbacterial gastroenteritis. Due to the lack of a robust and reproducible in vitro culture system and an appropriate animal model, the mechanism underlying HuNoV-caused diarrhea remains unknown. In the current study, we [...] Read more.
Human norovirus (HuNoV) is one of the major pathogens of acute nonbacterial gastroenteritis. Due to the lack of a robust and reproducible in vitro culture system and an appropriate animal model, the mechanism underlying HuNoV-caused diarrhea remains unknown. In the current study, we found that HuNoV transfection induced the expression of aquaporin 1 (AQP1), which was further confirmed in the context of virus infection, whereas the enterovirus EV71 (enterovirus 71) did not have such an effect. We further revealed that VP1, the major capsid protein of HuNoV, was crucial in promoting AQP1 expression. Mechanistically, HuNoV induces AQP1 production through the NF-κB signaling pathway via inducing the expression, phosphorylation and nuclear translocation of p65. By using a model of human intestinal epithelial barrier (IEB), we demonstrated that HuNoV and VP1-mediated enhancement of small molecule permeability is associated with the AQP1 channel. Collectively, we revealed that HuNoV induced the production of AQP1 by activating the NF-κB signaling pathway. The findings in this study provide a basis for further understanding the significance of HuNoV-induced AQP1 expression and the potential mechanism underlying HuNoV-caused diarrhea. Full article
(This article belongs to the Special Issue Human Norovirus)
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