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.

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.

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 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.

Persistence of human astrovirus in fresh and marine water

1997 ◽  
Vol 35 (11-12) ◽  
pp. 243-247 ◽  
Author(s):  
A. Bosch ◽  
R. M. Pintó ◽  
C. Villena ◽  
F. X. Abad
Keyword(s):  
Tap Water ◽  
Oral Route ◽  
Marine Water ◽  
Rt Pcr ◽  
Cell Infection ◽  
Cell Monolayers ◽  
Human Astroviruses ◽  
Bacterial Gastroenteritis ◽  
Human Astrovirus ◽  
Polymerase Chain

Large gastroenteritis outbreaks associated with astroviruses are being reported with increasing frequency suggesting that astrovirus may be an important agent of epidemic acute non-bacterial gastroenteritis in children and adults. In this study, a procedure, based on infection of CaCo-2 cell monolayers followed by reverse-transcription polymerase chain reaction, was developed to ascertain the persistence of infectious human astroviruses in tap and marine water at 4±1°C and 20±1°C. The adequacy of this methodology for monitoring the decay of infectious fastidious viruses was assessed by determining the survival of a cytocidal virus (poliovirus 1) concomitantly by MPNCU and cell infection plus RT-PCR. After 60d in dechlorinated tap water, the decay of astrovirus infectivity was lower than 2 logs at 4±1°C and around 3.6 logs at 20±1°C, while after 90d the titre reduction was around 3.3 and 4.3 logs at 4±1°C and 20±1°C respectively. In natural non-autoclaved seawater at 20°C, astrovirus showed a lower level of persistence. The possibility to acquire data on the survival of fastidious viruses in the environment opens new perspectives on the epidemiology of some health significant infections transmitted by the faecal-oral route.

scholarly journals Rotaviruses Associate with Distinct Types of Extracellular Vesicles

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 763
Author(s):  
Pavel Iša ◽  
Arianna Pérez-Delgado ◽  
Iván R. Quevedo ◽  
Susana López ◽  
Carlos F. Arias
Keyword(s):  
Extracellular Vesicles ◽  
Cell Entry ◽  
Viral Gastroenteritis ◽  
Rotavirus Infection ◽  
Viral Particles ◽  
Cell Release ◽  
Neutralizing Monoclonal Antibody ◽  
Protease Treatment ◽  
Infected Cells ◽  
Vesicle Secretion

Rotaviruses are the leading cause of viral gastroenteritis among children under five years of age. Rotavirus cell entry has been extensively studied; however, rotavirus cell release is still poorly understood. Specifically, the mechanism by which rotaviruses leave the cell before cell lysis is not known. Previous works have found rotavirus proteins and viral particles associated with extracellular vesicles secreted by cells. These vesicles have been shown to contain markers of exosomes; however, in a recent work they presented characteristics more typical of microparticles, and they were associated with an increase in the infectivity of the virus. In this work, we purified different types of vesicles from rotavirus-infected cells. We analyzed the association of virus with these vesicles and their possible role in promotion of rotavirus infection. We confirmed a non-lytic rotavirus release from the two cell lines tested, and observed a notable stimulation of vesicle secretion following rotavirus infection. A fraction of the secreted viral particles present in the cell supernatant was protected from protease treatment, possibly through its association with membranous vesicles; the more pronounced association of the virus was with fractions corresponding to cell membrane generated microvesicles. Using electron microscopy, we found different size vesicles with particles resembling rotaviruses associated from both- the outside and the inside. The viral particles inside the vesicles were refractory to neutralization with a potent rotavirus neutralizing monoclonal antibody, and were able to infect cells even without trypsin activation. The association of rotavirus particles with extracellular vesicles suggests these might have a role in virus spread.

scholarly journals Human cytomegalovirus serum neutralizing antibodies block virus infection of endothelial/epithelial cells, but not fibroblasts, early during primary infection

2008 ◽  
Vol 89 (4) ◽  
pp. 853-865 ◽  
Author(s):  
Giuseppe Gerna ◽  
Antonella Sarasini ◽  
Marco Patrone ◽  
Elena Percivalle ◽  
Loretta Fiorina ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Human Cytomegalovirus ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Human Fibroblasts ◽  
Cell Infection ◽  
Neutralizing Activity ◽  
Hyperimmune Globulin ◽  
Human Sera ◽  
Infected Cells

A panel of human sera exhibited a ≥128-fold higher neutralizing potency against a human cytomegalovirus (HCMV) clinical isolate propagated and tested in endothelial (or epithelial) cells than against the same virus infecting human fibroblasts. In a group of 18 primary infections, the reverse geometric mean titre was in the range of 10–15 in human fibroblasts within the first 3 months after the onset of infection, whereas the endothelial cell infection-neutralizing activity was already present within the first 10 days, reaching median levels of 122, 320 and 545 at respectively 30, 60 and 90 days after onset, then declining slowly. This difference was also confirmed in the majority of reactivated and remote HCMV infections, as well as in a hyperimmune globulin preparation. The antibody response to HCMV pUL131A, pUL130 and pUL128 locus products, which are required for endothelial/epithelial cell infection, provided a potential molecular basis for such a differential neutralizing activity. In addition, monoclonal/monospecific antibodies raised against the pUL131A, pUL130 and pUL128 proteins were found to display an inhibitory activity on HCMV plaque formation and HCMV leukocyte transfer from HCMV-infected cells. Hence, conventional determination of the neutralizing activity of human sera in fibroblasts is misleading. Antibodies to pUL131A, pUL130 and pUL128 appear to display a major HCMV-neutralizing and dissemination-inhibiting activity.

Studies of a Defective Measles Virus

1968 ◽  
Vol 26 ◽  
pp. 208-209
Author(s):  
R. M. McCombs ◽  
M. Benyesh-Melnick ◽  
J. P. Brunschwig
Keyword(s):  
Inclusion Bodies ◽  
Measles Virus ◽  
Giant Cells ◽  
Helical Structures ◽  
Thin Sections ◽  
Virus Particles ◽  
Extracellular Virus ◽  
Culture Cells ◽  
Infected Cells ◽  
Eosinophilic Inclusions

Measles virus is an agent that is capable of replicating in a number of different culture cells and generally causes the formation of multinucleated giant cells. As a result of infection, virus is released from the cells into the culture fluids and reinfection can be initiated by this cell-free virus. The extracellular virus has been examined by negative staining with phosphotungstic acid and has been shown to be a rather pleomorphic particle with a diameter of about 140 mμ. However, no such virus particles have been detected in thin sections of the infected cells. Rather, the only virus-induced structures present in the giant cells are eosinophilic inclusions (intracytoplasmic or intranuclear). These inclusion bodies have been shown to contain helical structures, resembling the nucleocapsid observed in negatively stained preparations.

COVID 19 – Eye Issues

2020 ◽  
Vol 5 (Special) ◽  
Keyword(s):  
Host Cell ◽  
Target Cell ◽  
Cell Receptor ◽  
Human Tissues ◽  
Type Ii ◽  
Cell Infection ◽  
Host Cell Receptor ◽  
Infected Cells ◽  
Cellular Entry

The coronavirus illness (COVID-19) is caused by a new recombinant SARS-CoV (SARS-CoV) virus (SARS-CoV-2). Target cell infection by SARS-CoV is mediated by the prickly protein of the coronavirus and host cell receptor, enzyme 2 converting angiotensin (ACE2) [3]. Similarly, a recent study suggests that cellular entry by SARS-CoV-2 is dependent on both ACE2 as well as type II transmembrane axial protease (TMPRSS2) [4]. This means that detection of ACE2 and PRSS2 expression in human tissues can predict potential infected cells and their respective effects in COVID-19 patients [1].

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