The mammary glands of cows abundantly display receptors for circulating avian H5 viruses

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Май 24, 2024

Abstract Influenza A viruses (IAV) from the H5N1 2.3.4.4b clade are circulating in dairy farms United States of America, and goat infections have also been reported. These ruminants were presumed not to be hosts for IAVs. Previously, IAV-positive mammalian species hunters scavengers, possibly getting infected while feeding on birds. It is now that circulate US cattle transmit through a mammary gland route, contrast transmission by aerosols via respiratory tract, although latter cannot excluded. The receptor display tract cows IAVs unknown. Here, we used recombinant HA proteins representing current classical H5 determine distribution IAV receptors tissues goats. Most sialome cow lined with sialic acid modifications such as N-glycolyl O-acetyl, which bound IAV. Interestingly, protein isolates significantly gland, whereas failed do so. Furthermore, 9-O-acetyl modification prominent all tested, 5-N-glycolyl not, resulting avian hemagglutinins. This could explain high levels virus found these milk, adding supporting data this possible route.

Язык: Английский

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The mammary glands of cows abundantly display receptors for circulating avian H5 viruses

Journal of Virology, Год журнала: 2024, Номер 98(11)

Опубликована: Окт. 10, 2024

ABSTRACT Influenza A viruses (IAVs) from the H5N1 2.3.4.4b clade are circulating in dairy farms USA.; ruminants were presumed not to be hosts for IAVs. Previously, IAV-positive mammalian species hunters and scavengers, possibly getting infected while feeding on birds. It is now recognized that circulate US cattle transmit through a mammary gland route, contrast transmission by aerosols via respiratory tract. The sialome cow tract so far solely defined using plant lectins. Here, we used recombinant HA proteins representing current classical H5 determine distribution of IAV receptors tissues cows. We complemented our study mapping glycan upper lower tracts horses pigs. Most lined with sialic acid modifications, such as N-glycolyl O-acetyl, which bound IAV. Interestingly, protein isolates significantly gland, whereas failed do so. Furthermore, 9-O-acetyl modification prominent all tested, 5-N-glycolyl not, resulting display avian hemagglutinins. This could explain high levels virus found these milk, adding supporting data this route. IMPORTANCE influenza viruses, usually affect birds, have been USA. Surprisingly, spreading among cows, there possibility they spread air but their milk glands. To understand better, studied how attaches cow’s glands specific viral proteins. cow-associated binds strongly glands, unlike older versions infecting might why suggesting new way spreading.

Язык: Английский

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Single-molecule imaging reveals allosteric stimulation of SARS-CoV-2 spike receptor binding domain by host sialic acid

Science Advances, Год журнала: 2024, Номер 10(29)

Опубликована: Июль 17, 2024

Conformational dynamics of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (S) mediate exposure binding site for cellular receptor, angiotensin-converting enzyme (ACE2). The N-terminal domain (NTD) S binds terminal sialic acid (SA) moieties on cell surface, but functional role this interaction in virus entry is unknown. Here, we report that NTD-SA enhances both S-mediated attachment and ACE2 binding. Through single-molecule Förster resonance energy transfer imaging individual trimers, demonstrate SA to NTD allosterically shifts conformational equilibrium, favoring enhanced ACE2-binding site. Antibodies target block binding, which contributes their mechanism neutralization. These findings inform mechanisms activation at surface.

Язык: Английский

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A Comparison of Conserved Features in the Human Coronavirus Family Shows That Studies of Viruses Less Pathogenic than SARS-CoV-2, Such as HCoV-OC43, Are Good Model Systems for Elucidating Basic Mechanisms of Infection and Replication in Standard Laboratories

Viruses, Год журнала: 2025, Номер 17(2), С. 256 - 256

Опубликована: Фев. 13, 2025

In 2021, at the height of COVID-19 pandemic, coronavirus research spiked, with over 83,000 original articles related to word "coronavirus" added online resource PubMed. Just 2 years later, in 2023, only 30,900 were added. While, irrefutably, funding drastically decreased, a possible explanation for decrease interest is that projects on SARS-CoV-2, causative agent COVID-19, halted due challenge establishing good cellular or animal model system. Most laboratories do not have capabilities culture SARS-CoV-2 'in house' as this requires Biosafety Level (BSL) 3 laboratory. Until recently, BSL laboratory endemic coronaviruses was arduous low cytopathic effect isolated cell infection models and lack means quantify viral loads. The purpose review article compare human provide an assessment latest techniques use coronaviruses-HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1-as lower-biosafety-risk more pathogenic coronaviruses-SARS-CoV-2, SARS-CoV, MERS-CoV.

Язык: Английский

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Defining diverse Spike-Receptor interactions involved in SARS-CoV-2 entry: Mechanisms and Therapeutic Opportunities

Virology, Год журнала: 2025, Номер unknown, С. 110507 - 110507

Опубликована: Март 1, 2025

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an enveloped RNA virus that caused the Disease 2019 (COVID-19) pandemic. The SARS-CoV-2 Spike glycoprotein binds to angiotensin converting enzyme (ACE2) on host cells facilitate viral entry. However, presence of in nearly all human organs - including those with little or no ACE2 expression suggests involvement alternative receptors. Recent studies have identified several cellular proteins and molecules influence entry through ACE2-dependent, ACE2-independent, inhibitory mechanisms. In this review, we explore how these receptors were identified, their patterns roles entry, impact infection. Additionally, discuss therapeutic strategies aimed at disrupting virus-receptor interactions mitigate COVID-19 pathogenesis.

Язык: Английский

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Virological Traits of the SARS-CoV-2 BA.2.87.1 Lineage

Vaccines, Год журнала: 2024, Номер 12(5), С. 487 - 487

Опубликована: Май 1, 2024

Transmissibility and immune evasion of the recently emerged, highly mutated SARS-CoV-2 BA.2.87.1 are unknown. Here, we report that efficiently enters human cells but is more sensitive to antibody-mediated neutralization than currently dominating JN.1 variant. Acquisition adaptive mutations might thus be needed for efficient spread in population.

Язык: Английский

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Human coronavirus HKU1 spike structures reveal the basis for sialoglycan specificity and carbohydrate-promoted conformational changes

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Май 5, 2025

The human coronavirus HKU1 uses both sialoglycoconjugates and the protein transmembrane serine protease 2 (TMPRSS2) as receptors. Carbohydrate binding leads to spike up conformation required for TMPRSS2 binding, an outcome suggesting a distinct mechanism driving fusion of viral host cell membranes. Nevertheless, conformational changes promoted by carbohydrate have not been fully elucidated basis HKU1's specificity remains unknown. Reported here are high resolution cryo-EM structures trimer in its apo form complex with moiety candidate receptor, 9-O-acetylated GD3 ganglioside. show that monomer can exist four discrete states progression through them would promote upon binding. We also six-amino-acid insert is determinant gangliosides containing α2-8-linked disialic acid shows weak affinity sialic acids found on decoy receptors such mucins.

Язык: Английский

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Insights into Glycobiology and the Protein-Glycan Interactome Using Glycan Microarray Technologies

Molecular & Cellular Proteomics, Год журнала: 2024, Номер unknown, С. 100844 - 100844

Опубликована: Сен. 1, 2024

Язык: Английский

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Cross-Reactivity of Human, Wild Boar, and Farm Animal Sera from Pre- and Post-Pandemic Periods with Alpha- and Βeta-Coronaviruses (CoV), including SARS-CoV-2

Viruses, Год журнала: 2023, Номер 16(1), С. 34 - 34

Опубликована: Дек. 23, 2023

Panels of pre- and post-pandemic farm animals, wild boar human sera, including sera able to neutralize SARS-CoV-2 in vitro, were tested serological tests determine their cross-reactivity with β- α-CoV originating from animals. Sera neutralization assays high ascending concentrations (up 1 × 104 TCID50 units/well) β-CoV Bovine coronavirus (BCV), SARS-CoV-2, porcine α-CoV-transmissible gastroenteritis virus (TGEV). In addition, for immunostaining cells infected hemagglutinating encephalomyelitis (PHEV). Testing revealed a significantly higher percentage BCV (78%) humans that had experienced infection (SARS-CoV-2 convalescent sera) than was observed pre-pandemic (37%). Also, 46% these neutralized the highest concentration (5 103 TCID50/well) tested, whereas only 9.6% did. Largely similar percentages staining PHEV-infected by panels sera. Furthermore, collected boars living near densely populated area The Netherlands also showed (43%) stronger this (21%) (28%) (20%) nature reserve park limited access public. High cows (100%), pigs 45%), sheep (36%) rabbits (60%). However, cross-neutralization restricted specific herds or farms. TGEV (68%) few (4.6%). None PHEV cross-reacting pre-pandemic, animal effectively vitro. Preexisting antibodies This boosted after infection, indicating activated “memory” antibody response against structurally related epitopes expressed on surface broad range heterologous CoV, isolated Further research is needed elucidate if symptomless environmental exposure another triggers such other free-living

Язык: Английский

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Viral envelope proteins fused to multiple distinct fluorescent reporters to probe receptor binding

Protein Science, Год журнала: 2024, Номер 33(4)

Опубликована: Март 27, 2024

Abstract Enveloped viruses carry one or multiple proteins with receptor‐binding functionalities. Functional receptors can be glycans, proteinaceous, both; therefore, recombinant protein approaches are instrumental in attaining new insights regarding viral envelope properties. Visualizing and measuring receptor binding typically entails antibody detection direct labeling, whereas fluorescent fusions attractive tools molecular biology. Here, we report a suite of distinct fusions, both N‐ C‐terminal, for influenza A virus hemagglutinins SARS‐CoV‐2 spike RBD. The contained three six barrels were applied directly to cells assess

Язык: Английский

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