High Seropositivity Rate of Neutralizing Antibodies to Astrovirus VA1 in Human Populations

Janowski, Andrew B.; Owen, Macee C.; Dudley, Holly; López, Tomás; Espinosa, Rafaela; Elvin‐Lewis, Memory; Colichón, A; Arias, Carlos F.; Burbelo, Peter D.; Wang, David

doi:10.1128/msphere.00484-21

Cited by 16 publications

(10 citation statements)

References 42 publications

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“…A previously described fluorescent focus forming assay (FFA) was used to quantify the infectious titer of VA1 in focus forming units per mL (FFU/mL). Caco-2 cells were seeded into 96- well plates 38 . Multi-step growth curves were completed using Caco-2 cells with samples collected at 1, 24, 48, and 96 hpi.…”

Section: Methodsmentioning

confidence: 99%

The highly conserved stem-loop II motif is important for the lifecycle of astroviruses but dispensable for SARS-CoV-2

Janowski

Jiang

Fujii

et al. 2022

Preprint

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The stem-loop II motif (s2m) is an RNA element present in viruses from divergent viral families, including astroviruses and coronaviruses, but its functional significance is unknown. We created deletions or substitutions of the s2m in astrovirus VA1 (VA1), classic human astrovirus 1 (HAstV1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For VA1, recombinant virus could not be rescued upon partial deletion of the s2m or substitutions of G-C base pairs. Compensatory substitutions that restored the G-C base-pair enabled recovery of VA1. For HAstV1, a partial deletion of the s2m resulted in decreased viral titers compared to wild-type virus, and reduced activity in a replicon system. In contrast, deletion or mutation of the SARS-CoV-2 s2m had no effect on the ability to rescue the virus, growth in vitro, or growth in Syrian hamsters. Our study demonstrates the importance of the s2m is virus-dependent.

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Section: Methodsmentioning

confidence: 99%

The highly conserved stem-loop II motif is important for the lifecycle of astroviruses but dispensable for SARS-CoV-2

Janowski

Jiang

Fujii

et al. 2022

Preprint

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“…Tus, our results suggest that the observed mutations in the capsid protein do not have the capacity to cause signifcant antigenic variation. Serological assays using the neutralization of the virus as a quantitative measurement of antibodies have been used to evaluate the extent of AstV infection among human and animal populations [32,33]. However, the poor growth of avian AstVs in cell culture has hampered the widespread use of this assay to test feld sera.…”

Section: Discussionmentioning

confidence: 99%

Detection and Characterization of Goose Astrovirus Infections in Hatcheries and Commercial Goose Flocks

Ren

Zhang

et al. 2023

Transboundary and Emerging Diseases

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Goose astrovirus (GoAstV) has frequently been isolated in China since it was first identified as the etiological agent of visceral gout in goslings in 2017. However, the actual prevalence of GoAstV infection and its economic impact on commercial goose production remain poorly characterized. Here, virus detection and serological testing were conducted to determine the extent of GoAstV infection in commercial goose flocks. We detected GoAstV RNA in 2% (6/300) of dead-in-shell embryos and day-old hatched goslings by RT-PCR, indicating vertical transmission under natural conditions. Using a virus neutralization test, GoAstV antibodies were detected in 41.7%–61.1% of serum samples from four commercial goose flocks, indicating that infections were common. To determine the virus types circulating in the commercial flocks, we isolated 15 GoAstVs from goose tissue samples from farms located in five provinces during 2018–2022. Genomic sequence analysis showed that all sequences were corresponded to GoAstV group 2 (GoAstV-2) but were assigned into three capsid subgroups based on sequence variations in the capsid protein. Representative isolates of capsid subgroups were also antigenically evaluated using cross-neutralization tests in LMH cell cultures. The antigenic relatedness values (R) calculated using the Horsfall formula were between 62% and 86%, indicating that no significant antigenic differences exist between the isolates. Our findings indicate that GoAstV-2 viruses are an important cause of fatal gout in goose flocks, as well as hatchery contamination in China.

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“…The cell membrane was then permeabilized with 0.2% Triton X-100 (Sigma) in PBS for 15 min at room temperature. Next, samples were immunostained using a monoclonal neutralizing antibody (2A2, ref (5)), followed by incubation with protein A coupled to peroxidase. Finally, the cells were washed twice with PBS and stained with 50 μl of a solution containing 1 mg/ml of 3-amino-9-ethyl carbazole (AEC), 0.04% H 2 O 2 , and sodium acetate buffer (50 mM, pH 5).…”

Section: Methodsmentioning

confidence: 99%

“…The most commonly associated astrovirus genotype in human neurological disease is VA1. A recent report on the seroprevalence of neutralizing antibodies from two cohorts of adult and pediatric serum samples found the seropositivity rate in adults to be approximately 77%, and it was concluded that a majority of humans are exposed to VA1 between 2 and 9 years of age (5).…”

Section: Introductionmentioning

confidence: 99%

The capsid precursor protein of astrovirus VA1 is proteolytically processed intracellularly

Aguilera-Flores

López²,

Sandoval-Jaime³

et al. 2022

Preprint

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Human astrovirus VA1 has been associated with neurological disease in immunocompromised patients, and its recent propagation in cell culture has opened the possibility to study its biology. Unlike classical human astroviruses, VA1 growth was found to be independent of trypsin during virus replication in vitro. In this work, we show that despite its independence on trypsin activation for cell infection, the VA1 capsid precursor protein, of 86 kDa (VP86), is processed intracellularly, and this proteolytic processing is important for astrovirus VA1 infectivity. Antibodies raised against different regions of the capsid precursor showed that the polyprotein can be processed starting at either its amino- or carboxy-terminal end, and they allowed us to identify that proteins of about 33 (VP33) and 38 (VP38) kDa constitute the core and the spike proteins of the mature infectious virus particles, respectively. The amino-terminal end of the spike protein was found to be Thr-348. Whether the protease involved in intracellular cleavage of the capsid precursor is of viral or cellular origin remains to be determined, but the cleavage is independent of caspases. Also, trypsin is able to degrade the capsid precursor but has no effect on VP34 and VP38 proteins when assembled into virus particles. These studies provide the basis for advancement of the knowledge of astrovirus VA1 cell entry and replication.

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High Seropositivity Rate of Neutralizing Antibodies to Astrovirus VA1 in Human Populations

Cited by 16 publications

References 42 publications

The highly conserved stem-loop II motif is important for the lifecycle of astroviruses but dispensable for SARS-CoV-2

The highly conserved stem-loop II motif is important for the lifecycle of astroviruses but dispensable for SARS-CoV-2

Detection and Characterization of Goose Astrovirus Infections in Hatcheries and Commercial Goose Flocks

The capsid precursor protein of astrovirus VA1 is proteolytically processed intracellularly

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