Norovirus replication, host interactions and vaccine advances

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide in all age groups and cause significant disease and economic burden globally. To date, no approved vaccines or antiviral therapies are available to treat or prevent HuNoV illness. Several candidate vaccines are in cl...

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Published in	Nature reviews. Microbiology Vol. 23; no. 6; pp. 385 - 401
Main Authors	Prasad, B. V. Venkataram, Atmar, Robert L., Ramani, Sasirekha, Palzkill, Timothy, Song, Yongcheng, Crawford, Sue E., Estes, Mary K.
Format	Journal Article
Language	English
Published	London Nature Publishing Group UK 01.06.2025 Nature Publishing Group
Subjects	631/250/590 631/326/596 631/535 692/4020/1503/1501 Antiviral agents Biology Biomedical and Life Sciences Caliciviridae Infections - immunology Caliciviridae Infections - prevention & control Caliciviridae Infections - virology Clinical trials Epitope mapping Gastroenteritis Gastroenteritis - prevention & control Gastroenteritis - virology Host-Pathogen Interactions Humans Immune response Infectious Diseases Innate immunity Life Sciences Medical Microbiology Metagenomics Microbiology Neutralization Norovirus Norovirus - genetics Norovirus - immunology Norovirus - physiology Organoids Pandemics Parasitology Pathogenesis Replication Review Article Vaccine Development Vaccines Viral Vaccines - immunology Virology Virus Replication Viruses
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ISSN	1740-1526 1740-1534 1740-1534
DOI	10.1038/s41579-024-01144-9

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Abstract	Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide in all age groups and cause significant disease and economic burden globally. To date, no approved vaccines or antiviral therapies are available to treat or prevent HuNoV illness. Several candidate vaccines are in clinical trials, although potential barriers to successful development must be overcome. Recently, significant advances have been made in understanding HuNoV biology owing to breakthroughs in virus cultivation using human intestinal tissue-derived organoid (or enteroid) cultures, advances in structural biology technology combined with epitope mapping and increased metagenomic sequencing. New and unexpected strain-specific differences in pandemic versus non-pandemic virus structures, replication properties and virus–host interactions, including host factors required for susceptibility to infection and pathogenesis, are discussed. In this Review, the authors highlight recent advances in human norovirus biology, including classification, strain-specific differences in cell entry and innate immune responses. They also highlight progress in virus replication, neutralization assays, structural biology and antiviral targets, as well as the status and challenges of vaccine development.
AbstractList	Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide in all age groups and cause significant disease and economic burden globally. To date, no approved vaccines or antiviral therapies are available to treat or prevent HuNoV illness. Several candidate vaccines are in clinical trials, although potential barriers to successful development must be overcome. Recently, significant advances have been made in understanding HuNoV biology owing to breakthroughs in virus cultivation using human intestinal tissue-derived organoid (or enteroid) cultures, advances in structural biology technology combined with epitope mapping and increased metagenomic sequencing. New and unexpected strain-specific differences in pandemic versus non-pandemic virus structures, replication properties and virus–host interactions, including host factors required for susceptibility to infection and pathogenesis, are discussed. Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide in all age groups and cause significant disease and economic burden globally. To date, no approved vaccines or antiviral therapies are available to treat or prevent HuNoV illness. Several candidate vaccines are in clinical trials, although potential barriers to successful development must be overcome. Recently, significant advances have been made in understanding HuNoV biology owing to breakthroughs in virus cultivation using human intestinal tissue-derived organoid (or enteroid) cultures, advances in structural biology technology combined with epitope mapping and increased metagenomic sequencing. New and unexpected strain-specific differences in pandemic versus non-pandemic virus structures, replication properties and virus-host interactions, including host factors required for susceptibility to infection and pathogenesis, are discussed.Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide in all age groups and cause significant disease and economic burden globally. To date, no approved vaccines or antiviral therapies are available to treat or prevent HuNoV illness. Several candidate vaccines are in clinical trials, although potential barriers to successful development must be overcome. Recently, significant advances have been made in understanding HuNoV biology owing to breakthroughs in virus cultivation using human intestinal tissue-derived organoid (or enteroid) cultures, advances in structural biology technology combined with epitope mapping and increased metagenomic sequencing. New and unexpected strain-specific differences in pandemic versus non-pandemic virus structures, replication properties and virus-host interactions, including host factors required for susceptibility to infection and pathogenesis, are discussed. Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide in all age groups and cause significant disease and economic burden globally. To date, no approved vaccines or antiviral therapies are available to treat or prevent HuNoV illness. Several candidate vaccines are in clinical trials, although potential barriers to successful development must be overcome. Recently, significant advances have been made in understanding HuNoV biology owing to breakthroughs in virus cultivation using human intestinal tissue-derived organoid (or enteroid) cultures, advances in structural biology technology combined with epitope mapping and increased metagenomic sequencing. New and unexpected strain-specific differences in pandemic versus non-pandemic virus structures, replication properties and virus–host interactions, including host factors required for susceptibility to infection and pathogenesis, are discussed.In this Review, the authors highlight recent advances in human norovirus biology, including classification, strain-specific differences in cell entry and innate immune responses. They also highlight progress in virus replication, neutralization assays, structural biology and antiviral targets, as well as the status and challenges of vaccine development. Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide in all age groups and cause significant disease and economic burden globally. To date, no approved vaccines or antiviral therapies are available to treat or prevent HuNoV illness. Several candidate vaccines are in clinical trials, although potential barriers to successful development must be overcome. Recently, significant advances have been made in understanding HuNoV biology owing to breakthroughs in virus cultivation using human intestinal tissue-derived organoid (or enteroid) cultures, advances in structural biology technology combined with epitope mapping and increased metagenomic sequencing. New and unexpected strain-specific differences in pandemic versus non-pandemic virus structures, replication properties and virus–host interactions, including host factors required for susceptibility to infection and pathogenesis, are discussed. In this Review, the authors highlight recent advances in human norovirus biology, including classification, strain-specific differences in cell entry and innate immune responses. They also highlight progress in virus replication, neutralization assays, structural biology and antiviral targets, as well as the status and challenges of vaccine development.
Author	Ramani, Sasirekha Prasad, B. V. Venkataram Song, Yongcheng Palzkill, Timothy Estes, Mary K. Atmar, Robert L. Crawford, Sue E.
AuthorAffiliation	2 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA 1 Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA 3 Department of Medicine, Baylor College of Medicine, Houston, TX, USA
AuthorAffiliation_xml	– name: 2 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA – name: 1 Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Houston, TX, USA – name: 3 Department of Medicine, Baylor College of Medicine, Houston, TX, USA
Author_xml	– sequence: 1 givenname: B. V. Venkataram orcidid: 0000-0002-1172-2071 surname: Prasad fullname: Prasad, B. V. Venkataram organization: Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Department of Molecular Virology and Microbiology, Baylor College of Medicine – sequence: 2 givenname: Robert L. surname: Atmar fullname: Atmar, Robert L. organization: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Department of Medicine, Baylor College of Medicine – sequence: 3 givenname: Sasirekha surname: Ramani fullname: Ramani, Sasirekha organization: Department of Molecular Virology and Microbiology, Baylor College of Medicine – sequence: 4 givenname: Timothy surname: Palzkill fullname: Palzkill, Timothy organization: Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine, Department of Molecular Virology and Microbiology, Baylor College of Medicine – sequence: 5 givenname: Yongcheng surname: Song fullname: Song, Yongcheng organization: Verna and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Baylor College of Medicine – sequence: 6 givenname: Sue E. surname: Crawford fullname: Crawford, Sue E. organization: Department of Molecular Virology and Microbiology, Baylor College of Medicine – sequence: 7 givenname: Mary K. orcidid: 0000-0002-4813-4249 surname: Estes fullname: Estes, Mary K. email: mestes@bcm.edu organization: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Department of Medicine, Baylor College of Medicine
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Snippet	Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide in all age groups and cause significant disease and economic burden...
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SubjectTerms	631/250/590 631/326/596 631/535 692/4020/1503/1501 Antiviral agents Biology Biomedical and Life Sciences Caliciviridae Infections - immunology Caliciviridae Infections - prevention & control Caliciviridae Infections - virology Clinical trials Epitope mapping Gastroenteritis Gastroenteritis - prevention & control Gastroenteritis - virology Host-Pathogen Interactions Humans Immune response Infectious Diseases Innate immunity Life Sciences Medical Microbiology Metagenomics Microbiology Neutralization Norovirus Norovirus - genetics Norovirus - immunology Norovirus - physiology Organoids Pandemics Parasitology Pathogenesis Replication Review Article Vaccine Development Vaccines Viral Vaccines - immunology Virology Virus Replication Viruses
Title	Norovirus replication, host interactions and vaccine advances
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