The molecular pathology of noroviruses Karst, Stephanie M; Zhu, Shu; Goodfellow, Ian G
Journal of pathology,
January 2015, Letnik:
235, Številka:
2
Journal Article
Norovirus is the leading cause of acute gastroenteritis worldwide. Since the discovery of human norovirus (HuNoV), an efficient and reproducible norovirus replication system has not been established ...in cultured cells. Although limited amounts of virus particles can be produced when the HuNoV genome is directly transfected into cells, the HuNoV cycle of infection has not been successfully reproduced in any currently available cell-culture system. Those results imply that the identification of a functional cell-surface receptor for norovirus might be the key to establishing a norovirus culture system. Using a genome-wide CRISPR/Cas9 guide RNA library, we identified murine CD300lf and CD300ld as functional receptors for murine norovirus (MNV). The treatment of susceptible cells with polyclonal antibody against CD300lf significantly reduced the production of viral progeny. Additionally, ectopic CD300lf expression in nonsusceptible cell lines derived from other animal species enabled MNV infection and progeny production, suggesting that CD300lf has potential for dictating MNV host tropism. Furthermore, CD300ld, which has an amino acid sequence in the N-terminal region of its extracellular domain that is highly homologous to that of CD300lf, also functions as a receptor for MNV. Our results indicate that direct interaction of MNV with two cell-surface molecules, CD300lf and CD300ld, dictates permissive noroviral infection.
Noroviruses are important human pathogens known to cause epidemic outbreaks of severe gastroenteritis in communities, military barracks, cruise ships, hospitals, and assisted living communities, ...resulting in over 267 000 000 annual infections worldwide. Diversity within the norovirus genus allows this virus to persist in human populations, although a single genocluster, the GII.4 noroviruses, currently accounts for ∼80% of all infections. Noroviruses bind to the polymorphic histoblood group antigens (HBGAs), which act as the putative cellular receptor, and strains from different genoclusters bind various HBGAs. Human challenge studies using viruses from different genoclusters have demonstrated that norovirus immunity is complicated and probably confounded by pre‐existing exposure histories and variable immune responses. Evidence for both short‐term and long‐term immunity has been demonstrated, but the molecular mechanisms mediating differential immune responses in the face of infection remain unclear. Studies with virus‐like particles from the GII.4 genocluster demonstrated that variation in and around the receptor‐binding domain results in differential HBGA binding and altered antigenicity. These observations suggest that the norovirus capsid evolves to evade the memory immune response while retaining its ability to bind any of several HBGAs. In this review, we discuss how evolution within the capsid drives receptor switching and allows escape from herd immunity.
PURPOSE OF REVIEWNoroviruses are a major cause of gastroenteritis. This review summarizes new information on noroviruses that may lead to the development of improved measures for limiting their human ...health impact.
RECENT FINDINGSGII.4 strains remain the most common human noroviruses causing disease, although GII.2 and GII.17 strains have recently emerged as dominant strains in some populations. Histo-blood group antigen (HBGA) expression on the gut mucosa drives susceptibility to different norovirus strains. Antibodies that block virus binding to these glycans correlate with protection from infection and illness. Immunocompromised patients are significantly impacted by norovirus infection, and the increasing availability of molecular diagnostics has improved infection recognition. Human noroviruses can be propagated in human intestinal enteroid cultures containing enterocytes that are a significant primary target for initiating infection. Strain-specific requirements for replication exist with bile being essential for some strains. Several vaccine candidates are progressing through preclinical and clinical development and studies of potential antiviral interventions are underway.
SUMMARYNorovirus epidemiology is complex and requires continued surveillance to track the emergence of new strains and recombinants, especially with the continued progress in vaccine development. Humans are the best model to study disease pathogenesis and prevention. New in-vitro cultivation methods should lead to better approaches for understanding virus-host interactions and ultimately to improved strategies for mitigation of human norovirus-associated disease.
Noroviruses are a major cause of sporadic cases and epidemic outbreaks of gastroenteritis. The development of molecular diagnostic assays has led to an increased recognition of the significance of ...these viruses as causes of gastroenteritis in all age groups. This article reviews the epidemiology, clinical manifestations and pathogenesis of norovirus infection, and it describes the diagnostic and therapeutic approaches to this disease.
Norovirus causes gastroenteritis in immunocompetent and immunocompromised hosts. It is the most common cause of gastroenteritis in U.S. adults seeking emergency department care. Genetic features and ...emerging treatments are discussed.
Infectious gastroenteritis is a common, acute illness that is characteristically self-limiting, but it can become debilitating and life-threatening in immunocompromised patients.
1
Noroviruses are major pathogens among the microbes associated with gastroenteritis in both immunocompetent and immunocompromised hosts
1
–
4
(Table 1). In the United States, noroviruses are the single most common cause of acute gastroenteritis in adults that results in a visit to the hospital emergency department,
2
and they are second only to rotaviruses as a major cause of severe diarrhea in infants and young children.
5
In developing countries, noroviruses are estimated to cause more than 200,000 deaths annually among children . . .
Norovirus is a leading cause of childhood vomiting and diarrhea in the United States and globally. Although most illnesses caused by norovirus are self-resolving, severe outcomes may occur from ...dehydration, including hospitalization and death. A vast majority of deaths from norovirus occur in developing countries. Immunocompromised children are at risk for more severe outcomes. Treatment of norovirus illness is focused on early correction of dehydration and maintenance of fluid status and nutrition. Hand hygiene, exclusion of ill individuals, and environmental cleaning are important for norovirus outbreak prevention and control, and vaccines to prevent norovirus illness are currently under development.
The Foodborne Viruses in Europe network has developed integrated epidemiological and virological outbreak reporting with aggregation and sharing of data through a joint database. We analyzed data ...from reported outbreaks of norovirus (NoV)-caused gastroenteritis from 13 European countries (July 2001 to July 2006) for trends in time and indications of different epidemiology of genotypes and variants. Of the 13 countries participating in this surveillance network, 11 were capable of collecting integrated epidemiological and virological surveillance data and 10 countries reported outbreaks throughout the entire period. Large differences in the numbers and rates of reported outbreaks per country were observed, reflecting the differences in the focus and coverage of national surveillance systems. GII.4 strains predominated throughout the 5-year surveillance period, but the proportion of outbreaks associated with GII.4 rose remarkably during years in which NoV activity was particularly high. Spring and summer peaks indicated the emergence of genetically distinct variants within GII.4 across Europe and were followed by increased NoV activity during the 2002-2003 and 2004-2005 winter seasons. GII.4 viruses predominated in health care settings and in person-to-person transmission. The consecutive emergence of new GII.4 variants is highly indicative of immune-driven selection. Their predominance in health care settings suggests properties that facilitate transmission in settings with a high concentration of people such as higher virus loads in excreta or a higher incidence of vomiting. Understanding the mechanisms driving the changes in epidemiology and clinical impact of these rapidly evolving RNA viruses is essential to design effective intervention and prevention measures.
Norovirus is known as the major cause of highly infection for gastrointestinal tracts. In this study, robust and highly sensitive biosensors for detecting human norovirus by employing a recognition ...affinity peptide-based electrochemical platform were described. A series of amino acid-substituted and cysteine-incorporated recognition peptides isolated from evolutionary phage display technique was chemically synthesized and immobilized to a gold sensor layer, the detection performance of the gold-immobilized synthetic peptide-based sensor system was assessed using QCM, CV and EIS. Using EIS, the limit of detection with Noro-1 as a molecular binder was found to be 99.8nM for recombinant noroviral capsid proteins (rP2) and 7.8copies/mL for human norovirus, thereby demonstrating a high degree of sensitivity for their corresponding targets. These results suggest that a biosensor which consists of affinity peptides as a molecular binder and miniaturized microdevices as diagnostic tool could be served as a new type of biosensing platform for point-of-care testing.
Display omitted
•An ultrasensitive and label-free electrochemical biosensor for human norovirus was developed.•The electrochemical detection was performance by CV, QCM and EIS.•The detection limit was found to be 7.8copies/mL.
PDF
