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Lancet (London, England) Jul 2018Enteric viruses, particularly rotaviruses and noroviruses, are a leading cause of gastroenteritis worldwide. Rotaviruses primarily affect young children, accounting for... (Review)
Review
Enteric viruses, particularly rotaviruses and noroviruses, are a leading cause of gastroenteritis worldwide. Rotaviruses primarily affect young children, accounting for almost 40% of hospital admissions for diarrhoea and 200 000 deaths worldwide, with the majority of deaths occurring in developing countries. Two vaccines against rotavirus were licensed in 2006 and have been implemented in 95 countries as of April, 2018. Data from eight high-income and middle-income countries showed a 49-89% decline in rotavirus-associated hospital admissions and a 17-55% decline in all-cause gastroenteritis-associated hospital admissions among children younger than 5 years, within 2 years of vaccine introduction. Noroviruses affect people of all ages, and are a leading cause of foodborne disease and outbreaks of gastroenteritis worldwide. Prevention of norovirus infection relies on frequent hand hygiene, limiting contact with people who are infected with the virus, and disinfection of contaminated environmental surfaces. Norovirus vaccine candidates are in clinical trials; whether vaccines will provide durable protection against the range of genetically and antigenically diverse norovirus strains remains unknown. Treatment of viral gastroenteritis is based primarily on replacement of fluid and electrolytes.
Topics: Adolescent; Adult; Aged; Caliciviridae Infections; Child; Child, Preschool; Cross-Sectional Studies; Developing Countries; Gastroenteritis; Humans; Infant; Middle Aged; Norovirus; Patient Admission; Rotavirus Infections; Rotavirus Vaccines; Viral Vaccines
PubMed: 30025810
DOI: 10.1016/S0140-6736(18)31128-0 -
Viruses Nov 2021Human 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"... (Review)
Review
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.
Topics: Antiviral Agents; COVID-19; Caliciviridae Infections; Gastroenteritis; Gastrointestinal Microbiome; Host-Pathogen Interactions; Humans; Norovirus; SARS-CoV-2; Viral Vaccines
PubMed: 34960668
DOI: 10.3390/v13122399 -
Viruses May 2021Laboratory cultivation of viruses is critical for determining requirements for viral replication, developing detection methods, identifying drug targets, and developing... (Review)
Review
Laboratory cultivation of viruses is critical for determining requirements for viral replication, developing detection methods, identifying drug targets, and developing antivirals. Several viruses have a history of recalcitrance towards robust replication in laboratory cell lines, including human noroviruses and hepatitis B and C viruses. These viruses have tropism for tissue components of the enterohepatic circulation system: the intestine and liver, respectively. The purpose of this review is to discuss how key enterohepatic signaling molecules, bile acids (BAs), and BA receptors are involved in the replication of these viruses and how manipulation of these factors was useful in the development and/or optimization of culture systems for these viruses. BAs have replication-promoting activities through several key mechanisms: (1) affecting cellular uptake, membrane lipid composition, and endocytic acidification; (2) directly interacting with viral capsids to influence binding to cells; and (3) modulating the innate immune response. Additionally, expression of the Na-taurocholate cotransporting polypeptide BA receptor in continuous liver cell lines is critical for hepatitis B virus entry and robust replication in laboratory culture. Viruses are capable of hijacking normal cellular functions, and understanding the role of BAs and BA receptors, components of the enterohepatic system, is valuable for expanding our knowledge on the mechanisms of norovirus and hepatitis B and C virus replication.
Topics: Bile; Bile Acids and Salts; Gastrointestinal Diseases; Hepatitis B virus; Humans; Liver; Norovirus; Virus Internalization; Virus Replication
PubMed: 34071855
DOI: 10.3390/v13060998 -
Cureus Aug 2018In contemporary medical practice, approaches to infectious disease management have been primarily rooted in a pathogen-centered model. However, host genetics also... (Review)
Review
In contemporary medical practice, approaches to infectious disease management have been primarily rooted in a pathogen-centered model. However, host genetics also contribute significantly to infectious disease burden. The fast expansion of bioinformatics techniques and the popularization of the genome-wide association study (GWAS) in recent decades have allowed for rapid and affordable high-throughput genomic analyses. This review focuses on the host model of infectious disease with particular emphasis placed on the genetic variations underlying observed infectious disease predisposition. First, we introduce observational twin-twin concordance studies of diseases such as poliomyelitis, tuberculosis, and hepatitis which suggest the important role of host genetics. We review the well-established links between specific genetic alterations and predisposition to malaria ( and ), Creutzfeldt-Jacob disease (CJD), human immunodeficiency virus (HIV), and Norwalk virus. Finally, we discuss the novel findings yielded by modern GWAS studies, which suggest the strong contribution of immunologic variation in the major histocompatibility complex (MHC) to host genetic infectious disease susceptibility. Future large-scale genomic studies hold promise in providing insights into immunology-pathogen links and may allow for the development of personalized genomic approaches to infectious disease prevention and treatment.
PubMed: 30405986
DOI: 10.7759/cureus.3210 -
Viruses Oct 2021Human norovirus (HuNoV) infection is a global health and economic burden. Currently, there are no licensed HuNoV vaccines or antiviral drugs available. The protease... (Review)
Review
Human norovirus (HuNoV) infection is a global health and economic burden. Currently, there are no licensed HuNoV vaccines or antiviral drugs available. The protease encoded by the HuNoV genome plays a critical role in virus replication by cleaving the polyprotein and is an excellent target for developing small-molecule inhibitors. The current strategy for developing HuNoV protease inhibitors is by targeting the enzyme's active site and designing inhibitors that bind to the substrate-binding pockets located near the active site. However, subtle differential conformational flexibility in response to the different substrates in the polyprotein and structural differences in the active site and substrate-binding pockets across different genogroups, hamper the development of effective broad-spectrum inhibitors. A comparative analysis of the available HuNoV protease structures may provide valuable insight for identifying novel strategies for the design and development of such inhibitors. The goal of this review is to provide such analysis together with an overview of the current status of the design and development of HuNoV protease inhibitors.
Topics: Animals; Antiviral Agents; Binding Sites; Caliciviridae Infections; Catalytic Domain; Drug Development; Genotype; Humans; Models, Molecular; Norovirus; Peptide Hydrolases; Polyproteins; Protease Inhibitors; Protein Conformation; Protein Interaction Domains and Motifs; Viral Proteins; Virus Replication
PubMed: 34696498
DOI: 10.3390/v13102069 -
Expert Review of Vaccines Mar 2010Noroviruses (NoV) cause the great majority of epidemic nonbacterial gastroenteritis in humans. Expression of the capsid protein in recombinant systems, including insect... (Review)
Review
Noroviruses (NoV) cause the great majority of epidemic nonbacterial gastroenteritis in humans. Expression of the capsid protein in recombinant systems, including insect and plant cells, yields assembly of virus-like particles (VLPs) that mimic the antigenic structure of authentic virions, and are relatively acid- and heat-stable. Norwalk virus (NV), the prototype NoV, has been studied extensively, and Norwalk virus-like particles (NVLPs) produced in insect cells and plants are immunogenic in mice and humans when delivered orally, stimulating the production of systemic and mucosal anti-NV antibodies. NVLPs are also highly immunogenic when delivered intranasally, provoking antibodies at levels similar to orally delivered VLP at much lower doses. Oral and nasal delivery of NVLPs efficiently produces antibodies at distal mucosal sites, which suggests that NVLPs could be used to deliver heterologous peptide antigens by production of genetic fusion chimeric capsid proteins. Examination of norovirus VLP surface structures and receptor binding motifs facilitates identification of potential sites for insertion of foreign peptides that will minimally affect the efficiency of VLP assembly and receptor binding. Thus, there is strong potential to use norovirus VLPs as vaccine-delivery vehicles.
Topics: Administration, Intranasal; Administration, Oral; Animals; Antibodies, Viral; Cell Line; Genetic Vectors; Humans; Immunity, Mucosal; Insecta; Mice; Norwalk virus; Plants; Recombinant Proteins; Vaccines, Virosome; Viral Proteins; Viral Vaccines
PubMed: 20218858
DOI: 10.1586/erv.09.163 -
Bailliere's Clinical Gastroenterology Jun 1993Increased knowledge has been gained into the aetiology and pathogenesis of viral gastroenteritis during the past two decades. There are now thought to be four major... (Review)
Review
Increased knowledge has been gained into the aetiology and pathogenesis of viral gastroenteritis during the past two decades. There are now thought to be four major subclassifications of gastroenteritis-causing viruses; these include rotavirus, enteric adenovirus, calicivirus, including Norwalk and Norwalk-like viruses, and astrovirus. The association of these agents with gastroenteritis has been made by their electron microscopic detection in stool and intestinal biopsy specimens from affected patients, the inability to detect the viruses after recovery from disease, and the subsequent development of immunoglobulin responses after infection; in some instances disease transmission was achieved in human volunteers. The association of these viral agents with gastroenteritis has facilitated the study of classification, epidemiology, immunity, diagnostic tests, methods of treatment and, most importantly, disease prevention strategies such as vaccine development for rotavirus. This chapter highlights the major features of these agents, with special attention being given to the pertinent molecular biology as well as current and future prospects for vaccination. Enteric viral infections of the gastrointestinal tract in patients with AIDS are also discussed.
Topics: Diarrhea; Gastroenteritis; Humans; Vaccination; Virus Diseases
PubMed: 8364245
DOI: 10.1016/0950-3528(93)90044-s -
Clinical Microbiology and Infection :... Apr 2003Acute gastroenteritis is one of the most common diseases in humans worldwide. Viruses are recognized as important causes of this disease, particularly in children. Since... (Review)
Review
Acute gastroenteritis is one of the most common diseases in humans worldwide. Viruses are recognized as important causes of this disease, particularly in children. Since the Norwalk virus was identified as a cause of gastroenteritis, the number of viral agents associated with diarrheal disease in humans has steadily increased. Rotavirus is the most common cause of severe diarrhea in children under 5 years of age. Astrovirus, calicivirus and enteric adenovirus are also important etiologic agents of acute gastroenteritis. Other viruses, such as toroviruses, coronaviruses, picobirnaviruses and pestiviruses, are increasingly being identified as causative agents of diarrhea. In recent years, the availability of diagnostic tests, mainly immunoassays or molecular biology techniques, has increased our understanding of this group of viruses. The future development of a safe and highly effective vaccine against rotavirus could prevent, at least, cases of severe diarrhea and reduce mortality from this disease.
Topics: Acute Disease; Caliciviridae; Coronavirus; Diarrhea; Gastroenteritis; Humans; Mamastrovirus; Picobirnavirus; Rotavirus; Torovirus; Virus Diseases; Viruses
PubMed: 12667234
DOI: 10.1046/j.1469-0691.2003.00560.x