scholarly journals Fecal Components Modulate Human Astrovirus Infectivity in Cells and Reconstituted Intestinal Tissues

mSphere ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Francisco J. Pérez-Rodriguez ◽  
Gael Vieille ◽  
Lara Turin ◽  
Soner Yildiz ◽  
Caroline Tapparel ◽  
...  
Keyword(s):  
Real Life ◽  
Enteric Viruses ◽  
Enteric Virus ◽  
Viral Gastroenteritis ◽  
Dependent Manner ◽  
Viral Genotype ◽  
Interindividual Differences ◽  
Human Astroviruses ◽  
Human Astrovirus

ABSTRACT Human astroviruses (HAstV) are among the most common causative agents of viral gastroenteritis, especially in children, and extraintestinal manifestations have also been described. These viruses are transmitted by the fecal-oral route, implying that stool composition and the gut microbiota may impact their ability to remain infectious. For some enteric viruses, individual bacterial envelope components and other polysaccharide-containing molecules, which are abundant in stools, have been shown to enhance capsid stability. However, the role of the complex stool environment and, most importantly, the role of interindividual differences have been poorly studied. We used HAstV as a model to investigate how the stool environment in itself, its interindividual variability, and some specific stool components could affect HAstV stability and infectivity. Using two different HAstV genotypes, we found that stools as a whole modulate astrovirus infectivity not only in an individual-dependent manner but also in a manner that depends on the viral genotype. A virus-protective effect was observed after incubation with various Gram-positive and Gram-negative bacteria as well as with bacterial components, such as lipopolysaccharide and peptidoglycan. These results were further confirmed in human intestinal tissues, a more physiologically relevant system. Astrovirus infectivity was also preserved by mucin, a major component of intestinal mucus. We further confirmed that these components stabilize the viral capsid. These results show that although HAstV benefits from the stabilizing effect of fecal components, the complexity and variability of the stool composition and the multiple potential interactions may explain the interindividual differences in viral transmission observed in real life. IMPORTANCE To ensure transmission, enteric viruses must maintain their infectivity during the various environmental challenges that they face in transit within and between hosts. Increased knowledge of the factors affecting enteric virus survival may help to control their transmission. This study reveals that specific fecal bacterial components preserve classic human astrovirus infectivity by stabilizing viral particles. However, the outcomes of stool-virus interactions are very variable, ranging from protection to a reduction of viral infectivity, depending on the viral genotype and the individual from whom the stool has been collected. We show that the transmissibility of enteric viruses is dependent on the intestinal contents of the infected individual and highlight the complex multiple interactions that could explain the stochastic nature of enteric virus transmission in humans.

scholarly journals Enteric Viruses and Inflammatory Bowel Disease

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 104
Author(s):  
Georges Tarris ◽  
Alexis de Rougemont ◽  
Maëva Charkaoui ◽  
Christophe Michiels ◽  
Laurent Martin ◽  
...  
Keyword(s):  
Association Studies ◽  
Enteric Viruses ◽  
Enteric Virus ◽  
Viral Gastroenteritis ◽  
Blood Group Antigens ◽  
Genome Wide Association Studies ◽  
Virus Infections ◽  
T Helper ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a multifactorial disease in which dietary, genetic, immunological, and microbial factors are at play. The role of enteric viruses in IBD remains only partially explored. To date, epidemiological studies have not fully described the role of enteric viruses in inflammatory flare-ups, especially that of human noroviruses and rotaviruses, which are the main causative agents of viral gastroenteritis. Genome-wide association studies have demonstrated the association between IBD, polymorphisms of the FUT2 and FUT3 genes (which drive the synthesis of histo-blood group antigens), and ligands for norovirus and rotavirus in the intestine. The role of autophagy in defensin-deficient Paneth cells and the perturbations of cytokine secretion in T-helper 1 and T-helper 17 inflammatory pathways following enteric virus infections have been demonstrated as well. Enteric virus interactions with commensal bacteria could play a significant role in the modulation of enteric virus infections in IBD. Based on the currently incomplete knowledge of the complex phenomena underlying IBD pathogenesis, future studies using multi-sampling and data integration combined with new techniques such as human intestinal enteroids could help to decipher the role of enteric viruses in IBD.

scholarly journals Human Astrovirus 1–8 Seroprevalence Evaluation in a United States Adult Population

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 979
Author(s):  
Lena Meyer ◽  
Kevin Delgado-Cunningham ◽  
Nicholas Lorig-Roach ◽  
Jordan Ford ◽  
Rebecca M. DuBois
Keyword(s):  
United States ◽  
Adult Population ◽  
Neutralizing Antibody ◽  
Viral Gastroenteritis ◽  
Igg Antibodies ◽  
Cross Sectional ◽  
Human Astroviruses ◽  
Serotype 1 ◽  
Serotype 5 ◽  
Human Astrovirus

Human astroviruses are an important cause of viral gastroenteritis globally, yet few studies have investigated the serostatus of adults to establish rates of previous infection. Here, we applied biolayer interferometry immunosorbent assay (BLI-ISA), a recently developed serosurveillance technique, to measure the presence of blood plasma IgG antibodies directed towards the human astrovirus capsid spikes from serotypes 1–8 in a cross-sectional sample of a United States adult population. The seroprevalence rates of IgG antibodies were 73% for human astrovirus serotype 1, 62% for serotype 3, 52% for serotype 4, 29% for serotype 5, 27% for serotype 8, 22% for serotype 2, 8% for serotype 6, and 8% for serotype 7. Notably, seroprevalence rates for capsid spike antigens correlate with neutralizing antibody rates determined previously. This work is the first seroprevalence study evaluating all eight classical human astrovirus serotypes.

scholarly journals Characterizing a Murine Model for Astrovirus Using Viral Isolates from Persistently Infected Immunocompromised Mice

2019 ◽  
Vol 93 (13) ◽  
Author(s):  
Valerie Cortez ◽  
Bridgett Sharp ◽  
Jiangwei Yao ◽  
Brandi Livingston ◽  
Peter Vogel ◽  
...  
Keyword(s):  
Animal Model ◽  
Small Animal ◽  
Enteric Viruses ◽  
Mouse Strains ◽  
Wild Type ◽  
Small Animal Model ◽  
Human Astroviruses ◽  
Duration Of Infection ◽  
Human Astrovirus ◽  
Immunocompromised Mice

ABSTRACT Human astroviruses are single-stranded RNA enteric viruses that cause a spectrum of disease ranging from asymptomatic infection to systemic extragastrointestinal spread; however, they are among the least-characterized enteric viruses, and there is a lack of a well-characterized small animal model. Finding that immunocompromised mice were resistant to human astrovirus infection via multiple routes of inoculation, our studies aimed to determine whether murine astrovirus (MuAstV) could be used to model human astrovirus disease. We experimentally infected wild-type mice with MuAstV isolated from immunocompromised mice and found that the virus was detected throughout the gastrointestinal tract, including the stomach, but was not associated with diarrhea. The virus was also detected in the lung. Although virus levels were higher in recently weaned mice, the levels were similar in male and female adult mice. Using two distinct viruses isolated from different immunocompromised mouse strains, we observed virus strain-specific differences in the duration of infection (3 versus 10 weeks) in wild-type mice, indicating that the within-host immune pressure from donor mice shaped the virus kinetics in immunocompetent recipient hosts. Both virus strains elicited minimal pathology and a lack of sustained immunity. In summary, MuAstV represents a useful model for studying asymptomatic human infection and gaining insight into the astrovirus pathogenesis and immunity. IMPORTANCE Astroviruses are widespread in both birds and mammals; however, little is known about the pathogenesis and the immune response to the virus due to the lack of a well-characterized small-animal model. Here we describe two distinct strains of murine astrovirus that cause infections in immunocompetent mice that mirror aspects of asymptomatic human infections, including minimal pathology and short-lived immunity. However, we noted that the duration of infection differed greatly between the strains, highlighting an important facet of these viruses that was not previously appreciated. The ubiquitous nature and diversity of murine astroviruses coupled with the continuous likelihood of reinfection raise the possibility of viral interference with other mouse models of disease.

scholarly journals Structures of Two Human Astrovirus Capsid/Neutralizing Antibody Complexes Reveal Distinct Epitopes and Inhibition of Virus Attachment to Cells

2021 ◽  
Author(s):  
Lena Ricemeyer ◽  
Nayeli Aguilar-Hernández ◽  
Tomás López ◽  
Rafaela Espinosa ◽  
Sarah Lanning ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Host Cells ◽  
Viral Gastroenteritis ◽  
Receptor Binding Site ◽  
Virus Attachment ◽  
Human Astroviruses ◽  
Human Astrovirus

Human astrovirus is an important cause of viral gastroenteritis worldwide. Young children, the elderly, and the immunocompromised are especially at risk for contracting severe disease. However, no vaccines exist to combat human astrovirus infection. Evidence points to the importance of antibodies in enabling protection of healthy adults from reinfection. To develop an effective subunit vaccine that broadly protects against diverse astrovirus serotypes, we must understand how neutralizing antibodies target the capsid surface at the molecular level. Here, we report the structures of the human astrovirus capsid spike domain bound to two neutralizing monoclonal antibodies. These antibodies bind two distinct conformational epitopes on the spike surface. We add to existing evidence that the human astrovirus capsid spike contains a receptor-binding domain and demonstrate that both antibodies neutralize human astrovirus by blocking virus attachment to host cells. We identify patches of conserved amino acids that overlap or border the antibody epitopes and may constitute a receptor-binding site. Our findings provide a basis to develop therapies that prevent and treat human astrovirus gastroenteritis. Importance Human astroviruses infect nearly every person in the world during childhood and cause diarrhea, vomiting, and fever. Despite the prevalence of this virus, little is known about how antibodies block virus infection. Here, we determined crystal structures of the astrovirus capsid protein in complex with two virus-neutralizing antibodies. We show that the antibodies bind two distinct sites on the capsid spike domain; however, both antibodies block virus attachment to human cells. Importantly, our findings support the use of the human astrovirus capsid spike as an antigen in a subunit-based vaccine to prevent astrovirus disease.

Molecular Detection of Enteric Viruses in Under-Five Children with Diarrhea in Debre Tabore, Northwest Ethiopia

2021 ◽  
Author(s):  
Aschalew Gelaw ◽  
Uwe G. Liebert
Keyword(s):  
Genetic Diversity ◽  
Enteric Viruses ◽  
Enteric Virus ◽  
Sub Saharan Africa ◽  
Small Data ◽  
Viral Gastroenteritis ◽  
Data Set ◽  
Fecal Samples ◽  
Under Five ◽  
Under Five Children

Abstract Viral gastroenteritis belongs to the major public health problems of infant and children worldwide. The largest proportion of morbidity and mortality occurs in Sub-Saharan Africa. This preliminary study aimed to assess the burden and genetic diversity of enteric viruses among children with diarrhea in Debre Tabore. A cross-sectional study was undertaken from December 2015 to April 2016. A total of thirty-eight children, who presented with diarrhea at Debre Tabore health centers were included. Fecal samples were collected and screened for enteric viruses by RT-PCR. Data were analyzed by using SPSS statistical software. Descriptive statistical summary techniques were used to display the study findings. Out of the thirty-eight children screened, 52.6% were positive for at least one enteric virus. Six (30.0%) of the children had mixed enteric virus infections. Human adenovirus (HAdV) 7 (18.4%) was predominant followed by noroviruses 5 (13.2%), enterovirus 5 (13.2%), rotavirus 4 (10.5%), human astrovirus (HAstV) 2 (5.3%), and human parechovirus (HPeV) 1(2.6%). Overall nineteen different types of enteric virus genotypes were identified. Diverse adenovirus within species A (HAdV-12,-31), B (HAdV-3), C (HAdV-2), and F (HAdV-4) were detected. Norovirus II (GII.4 and GII.6) and norovirus I (GI.2, GI.3, and GI.5) genotypes were found. Sapovirus genotypes within genogroup II (GII.1, GII.5, and GII.6) were identified. Wild-type rotavirus G9[P8] genotype was detected in one of the rotavirus positive samples. Non-polio enteroviruses within species A (coxsackie A virus (CAV) 5, CAV6, and CAV14) and C (enterovirus (EV-C) 99) were also identified. HPeV-6 genotype was identified in one of the samples. In two of the fecal samples, classic HAstV-2 was detected. Phylogenetic analysis of these enteric viruses revealed that they have close phylogenetic relatedness with previous genotypes reported from Ethiopia. Diverse enteric viruses were detected in fecal samples from under-five children with diarrhea. The detection of heterogeneous enteric viruses in this small data set highlights the need for extended multicenter studies to describe the burden and genetic diversity.

First detection of human astrovirus in gastroenteritis outbreak in Hungary

2011 ◽  
Vol 152 (2) ◽  
pp. 45-50 ◽  
Author(s):  
Péter Pankovics ◽  
Ákos Boros ◽  
Melinda Rovács ◽  
Erika Nagy ◽  
Erika Krisztián ◽  
...  
Keyword(s):  
Nucleotide Sequence ◽  
Care Center ◽  
Epidemiological Data ◽  
Oral Route ◽  
Viral Gastroenteritis ◽  
Gastroenteritis Outbreak ◽  
Etiological Role ◽  
Human Astroviruses ◽  
Stool Samples

Human astroviruses are one of the known pathogens of gastroenteritis in infants, children and rarely in elderly. It causes 4.2-7.3% of the sporadic gastroenteritis cases with diarrhea and vomiting in children. The etiological role of astrovirus has not been confirmed yet in outbreaks of gastroenteritis in Hungary. Aims: The first description of the detection and molecular epidemiology of astrovirus in outbreaks of gastroenteritis in Hungary. Materials and methods: Stool samples originated from Komárom-Esztergom County, from a day-care center (nursery) where a gastroenteritis outbreak occurred in June, 2010. Astrovirus was detected by RT-PCR methods. The nucleotide sequence of the nearly complete genome was sequenced. Clinical and epidemiological data were collected by epidemiological investigation. Results: Out of the 29 exposed persons (24 children and 5 adults) 7 (24.1%) children had gastroenteritis with diarrhea, and vomiting in one case, in the period of June 4-15, 2010. Bacterial pathogens, rotavirus, adenovirus and norovirus were not detected, but genotype 1 astrovirus could be identified in 3 (42.8%) stool samples (HQ398856). The nucleotide sequence of the astrovirus ORF1a/ORF1b/ORF2/3’UTR regions was determined. The source of the outbreak was presumably the firstly recognized ill child and the virus was spread by fecal-oral route with direct contact in the children community. Conclusions: Epidemiologic and clinical characteristics of the astrovirus outbreak in the nursery are described in details to prove that the possible etiological role of astroviruses in viral gastroenteritis which should not forget in order after rotaviruses, caliciviruses (norovirus and sapovirus) and enteric adenoviruses. Orv. Hetil., 2011, 152, 45–50.

scholarly journals Multiple novel astrovirus species in human stool

2009 ◽  
Vol 90 (12) ◽  
pp. 2965-2972 ◽  
Author(s):  
A. Kapoor ◽  
L. Li ◽  
J. Victoria ◽  
B. Oderinde ◽  
C. Mason ◽  
...  
Keyword(s):  
Developing Countries ◽  
Genetic Distance ◽  
Complete Genome ◽  
Rt Pcr ◽  
Rna Sequences ◽  
Human Astroviruses ◽  
Human Astrovirus ◽  
Stool Samples ◽  
Human Stool

Diarrhoea remains a significant cause of morbidity and mortality in developing countries where numerous cases remain without identified aetiology. Astroviruses are a recently identified cause of animal gastroenteritis which currently includes two species suspected of causing human diarrhoea. Using pan-astrovirus RT-PCR, we analysed human stool samples from different continents for astrovirus-related RNA sequences. We identified variants of the two known human astrovirus species plus, based on genetic distance criteria, three novel astrovirus species all distantly related to mink and ovine astroviruses, which we provisionally named HMOAstV species A–C. The complete genome of species A displayed all the conserved characteristics of mammalian astroviruses. Each of the now three groups of astroviruses found in human stool (HAstV, AstV-MLB and HMOAstV) were more closely related to animal astroviruses than to each other, indicating that human astroviruses may periodically emerge from zoonotic transmissions. Based on the pathogenic impact of their closest phylogenetic relatives in animals, further investigations of the role of HMOAstV, so far detected in Nigeria, Nepal and Pakistan, in human gastroenteritis are warranted.

scholarly journals Presence and Diversity of Different Enteric Viruses in Wild Norway Rats (Rattus norvegicus)

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 992
Author(s):  
Sandra Niendorf ◽  
Dominik Harms ◽  
Katja F. Hellendahl ◽  
Elisa Heuser ◽  
Sindy Böttcher ◽  
...  
Keyword(s):  
Enteric Viruses ◽  
Hepatitis E ◽  
High Detection Rate ◽  
Entire Genome ◽  
Group A ◽  
Human Astrovirus ◽  
Coxsackievirus A20 ◽  
Transmission Pathways ◽  
Norway Rats

Rodents are common reservoirs for numerous zoonotic pathogens, but knowledge about diversity of pathogens in rodents is still limited. Here, we investigated the occurrence and genetic diversity of enteric viruses in 51 Norway rats collected in three different countries in Europe. RNA of at least one virus was detected in the intestine of 49 of 51 animals. Astrovirus RNA was detected in 46 animals, mostly of rat astroviruses. Human astrovirus (HAstV-8) RNA was detected in one, rotavirus group A (RVA) RNA was identified in eleven animals. One RVA RNA could be typed as rat G3 type. Rat hepatitis E virus (HEV) RNA was detected in five animals. Two entire genome sequences of ratHEV were determined. Human norovirus RNA was detected in four animals with the genotypes GI.P4-GI.4, GII.P33-GII.1, and GII.P21. In one animal, a replication competent coxsackievirus A20 strain was detected. Additionally, RNA of an enterovirus species A strain was detected in the same animal, albeit in a different tissue. The results show a high detection rate and diversity of enteric viruses in Norway rats in Europe and indicate their significance as vectors for zoonotic transmission of enteric viruses. The detailed role of Norway rats and transmission pathways of enteric viruses needs to be investigated in further studies.

scholarly journals Wide Diversity of Recombinant Noroviruses Circulating in Spain, 2016 to 2020

2021 ◽  
Author(s):  
Noemi Navarro-Lleó ◽  
Cristina Santiso-Bellón ◽  
Susana Vila-Vicent ◽  
Noelia Carmona-Vicente ◽  
Roberto Gozalbo-Rovira ◽  
...  
Keyword(s):  
Enteric Virus ◽  
Viral Gastroenteritis ◽  
Junction Region ◽  
Predominant Genotype ◽  
Recombinant Strains ◽  
High Prevalence ◽  
Positive Rate ◽  
Sporadic Cases ◽  
Stool Samples

Noroviruses are the leading cause of sporadic cases and outbreaks of viral gastroenteritis. For more than 20 years most norovirus infections have been caused by the pandemic genotype GII.4, yet recent studies have reported the emergence of recombinant strains in many countries. In the present study, 4,950 stool samples collected between January 2016 and April 2020 in Valencia (Spain) from patients with acute gastroenteritis were analyzed to investigate the etiological agent. Norovirus was the most frequently detected enteric virus with a positive rate of 9.5% (471/4,950). Among 224 norovirus strains characterized, 175 belonged to genogroup GII and 49 to genogroup GI. Using dual genotyping based on sequencing the ORF1/ORF2 junction region we detected 25 different capsid-polymerase type associations. The most common GII capsid genotype was GII.4 Sydney 2012, followed by GII.2, GII.3, GII.6 and GII.17. A high prevalence of recombinant strains (90.4%) was observed among GII infections between 2018 and 2020. GII.4 Sydney[P16] was the predominant genotype from 2019 to 2020. In addition, GII.P16 polymerase was found harboring within six different capsid genes. A new subcluster of GII.4 Sydney associated with the P31 polymerase was identified by phylogenetic analysis. GI.4 and GI.3 were the predominant genotypes in genogroup GI, in which recombinant strains were also found, such as GI.3[P10], GI.3[P13] and GI.5[P4]. Interestingly, the GI.3[P10] strain could represent a new capsid genotype. This study shows the extensive diversity of recombinant noroviruses circulating in Spain and highlights the role of recombination events in the spread of noroviruses.

scholarly journals The association of human astrovirus with extracellular vesicles facilitates cell infection and protects the virus from neutralizing antibodies

2021 ◽  
Author(s):  
Carlos Baez-N ◽  
Ivan Rafael Quevedo ◽  
Susana López ◽  
Carlos Federico Arias ◽  
Pavel Isa
Keyword(s):  
Extracellular Vesicles ◽  
Neutralizing Antibodies ◽  
Viral Gastroenteritis ◽  
Cell Infection ◽  
Extracellular Virus ◽  
The Third ◽  
Human Astroviruses ◽  
Human Astrovirus ◽  
Infected Cells ◽  
Children Under 5

Viral gastroenteritis has a global distribution and represents a high risk for vulnerable population and children under 5 years because of acute diarrhea, fever and dehydration. Human astroviruses (HAstV) have been identified as the third most important cause of viral gastroenteritis in pediatric and immunocompromised patients. Furthermore, HAstV has been reported in biopsies taken from patients with encephalitis, meningitis and acute respiratory infection, yet it is not clear how the virus reaches these organs. In this work we tested the possibility that the released astrovirus particles could be associated with extracellular vesicles. Comparison between vesicles purified from astrovirus- and mock-infected cells showed that infection with HAstV Yuc8 enhances production of vesicles larger than 150 nm. These vesicles contain CD63 and Alix, two markers of vesicular structures. Some of the extracellular virus was found associated with vesicular membranes, and this association facilitates cell infection in the absence of trypsin activation and protects virions from neutralizing antibodies. Our findings suggest a new pathway for HAstV spread and might represent an explanation for the extraintestinal presence of some astrovirus strains.

Sign in / Sign up

Export Citation Format

Share Document