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HCOV-NL63 spike protein glycopeptides

ABSTRACT: HCoV-NL63 is a coronavirus that can cause severe lower respiratory tract infections requiring hospitalization. Of great interest is understanding the HCoV-NL63 coronavirus spike glycoprotein trimer, which is the conformational machine responsible for entry into host cells and the sole target of neutralizing antibodies during infection. We utilized an electron-transfer/higher energy collision dissociation ion fragmentation scheme (Frese, C. K. et al., 2013.) in combination with cryo-electron microscopy to resolve the extensive glycan shield that obstructs the protein surface. These glycans provide a structural framework to understanding the accessibility of the protein to antibodies.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Human Coronavirus Nl63

SUBMITTER: Joost Snijder

LAB HEAD: David Veesler

PROVIDER: PXD004557 | Pride | 2016-09-27

REPOSITORIES: Pride

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Glycan shield and epitope masking of a coronavirus spike protein observed by cryo-electron microscopy.

Walls Alexandra C AC Tortorici M Alejandra MA Frenz Brandon B Snijder Joost J Li Wentao W Rey Félix A FA DiMaio Frank F Bosch Berend-Jan BJ Veesler David D

Nature structural & molecular biology 20160912 10

The threat of a major coronavirus pandemic urges the development of strategies to combat these pathogens. Human coronavirus NL63 (HCoV-NL63) is an α-coronavirus that can cause severe lower-respiratory-tract infections requiring hospitalization. We report here the 3.4-Å-resolution cryo-EM reconstruction of the HCoV-NL63 coronavirus spike glycoprotein trimer, which mediates entry into host cells and is the main target of neutralizing antibodies during infection. The map resolves the extensive glyc ...[more]

PMID: 27617430

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A hinge glycan regulates spike bending and impacts coronavirus infectivity

Project description:Analysis of the structures and distributions of native spike conformations on vitrified human coronavirus NL63 (HCoV-NL63) virions without chemical fixation by cryogenic electron tomography (cryoET) and subtomogram averaging, along with site-specific glycan composition and occupancy determined by mass spectroscopy

2024-01-26 | PXD039247 | Pride

Cell host-response to infection with novel human coronavirus EMC predict potential antivirals and important differences with SARS-coronavirus.

Project description:Differential expression was determined in Calu-3 cells between mock infected and infection with either Human coronavirus EMC and SARS coronavirus at different times post infection. Calu-3 2B4 cells were infected with Human Coronavirus EMC 2012 (HCoV-EMC) or mock infected. Samples were collected 0, 3, 7, 12, 18 and 24 hpi. There are 3 mock and 3 infected replicates for each time point, except for 12 hpi for which there are only 2 infected replicates (one replicate did not pass RNA quality check). There were no mock sampes at 18 hpi, and therefore infected samples at 18 hpi were compared with mocks at 24 hpi. For direct comparison with SARS-CoV infected cells, raw data from HCoV-EMC experiments were quantile normalized together with the SARS-CoV dataset (GEO Series accession number GSE33267).

2013-05-03 | E-GEOD-45042 | biostudies-arrayexpress

N-terminomics for the identification of in-vitro substrates and cleavage site specificity of the SARS-CoV-2 main protease

Project description:The genome of coronaviruses, including the SARS-CoV-2, which causes the human pandemic COVID-19, encodes for two proteases, a papain like (PL) and the so-called Main protease (Mpro), also named 3CLpro or non-structural protein 5 (NSP5). Mpro is activated by autoproteolysis, and true to its name, is the main protease responsible for cutting the viral polyprotein into functional viral proteins. Aside from this function, it has been described that 3CL proteases are also capable to process host proteins, including those involved in the host innate immune response. We performed a LC-MS based N-terminomics analysis to identify in vitro substrates of three different recombinantly expressed coronavirus main proteases (SARS-CoV, SARS-CoV-2, hCoV-NL63) using lung cell lysates as substrate pools.

2020-11-02 | PXD021406 | Pride

Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors

Project description:The ongoing SARS-CoV-2 pandemic has devastated the global economy and claimed more than one million lives, presenting an urgent global health crisis. To identify host factors required for infection by SARS-CoV-2 and seasonal coronaviruses, we designed a focused high-coverage CRISPR-Cas9 library targeting 332 members of a recently published SARS-CoV-2 protein interactome. We leveraged the compact nature of this library to systematically screen SARS-CoV-2 at two physiologically relevant temperatures (33 ºC and 37 ºC) along with three related coronaviruses (HCoV-229E, HCoV-NL63, and HCoV-OC43), allowing us to probe this interactome at a much higher resolution relative to genome scale studies. This approach yielded several new insights, including unexpected virus-specific differences in Rab GTPase requirements and GPI anchor biosynthesis, as well as identification of multiple pan-coronavirus factors involved in cholesterol homeostasis. This coronavirus essentiality catalog could inform ongoing drug development efforts aimed at intercepting and treating COVID-19, and help prepare for future coronavirus outbreaks.

2020-11-24 | GSE162039 | GEO

HCOV-NL63 spike protein glycopeptides

Project description:HCoV-NL63 is a coronavirus that can cause severe lower respiratory tract infections requiring hospitalization. Of great interest is understanding the HCoV-NL63 coronavirus spike glycoprotein trimer, which is the conformational machine responsible for entry into host cells and the sole target of neutralizing antibodies during infection. We utilized an electron-transfer/higher energy collision dissociation ion fragmentation scheme (Frese, C. K. et al., 2013.) in combination with cryo-electron microscopy to resolve the extensive glycan shield that obstructs the protein surface. These glycans provide a structural framework to understanding the accessibility of the protein to antibodies.

2020-03-13 | MSV000085098 | MassIVE

Cytokine stimulation systems approach demonstrates differences in innate and pro-inflammatory host responses between genetically distinct MERS-CoV isolates.

Project description:Background: The recent emergence of a novel coronavirus in the Middle East (designated MERS-CoV) is a reminder of the zoonotic potential of coronaviruses and the severe disease these etiologic agents can cause in humans. Clinical features of Middle East respiratory syndrome (MERS) include severe acute pneumonia and renal failure that is highly reminiscent of severe acute respiratory syndrome (SARS) caused by SARS-CoV. The host response is a key component of highly pathogenic respiratory virus infection. Here, we computationally analyzed gene expression changes in a human airway epithelial cell line infected with two genetically distinct MERS-CoV strains obtained from human patients, MERS-CoV-EMC (designated EMC) and MERS-CoV-London (designated LoCoV). Results: Using topological techniques, such as persistence homology and filtered clustering, we characterized the host response system to the different MERS-CoVs, with LoCoV inducing early kinetic changes, between 3 and 12 hours post infection, compared to EMC. Robust transcriptional changes distinguished the two MERS-CoV strains predominantly at the late time points. Combining statistical analysis of infection and cytokine-stimulated treatment transcriptomics, we identified differential innate and pro-inflammatory responses between the two virus strains, including up-regulation of extracellular remodeling genes following LoCoV infection and differential pro-inflammatory responses between the two strains. Conclusions: These transcriptional differences may be the result of amino acid differences in viral proteins known to modulate innate immunity against MERS infection. Triplicate wells of Calu-3 2B4 cells were infected with Human Coronavirus EMC 2012 (HCoV-EMC) or time-matched mock infected. Cells were harvested at 0, 3, 7, 12, 18 and 24 hours post-infection (hpi), RNA extracted and transcriptomics analyzed by microarray.

2014-08-31 | E-GEOD-56677 | biostudies-arrayexpress

Transcriptomic profiling of human corona virus (HCoV)-229E -infected human cells

Project description:Human coronaviruses (HCoVs) cause mild to severe respiratory infection. Most of the common cold illnesses are caused by one of four HCoVs, namely HCoV-229E, HCoV-NL63, HCoV-HKU1 and HCoV-OC43. Several studies have applied global transcriptomic methods to understand host responses to HCoV infection, with most studies focusing on the pandemic severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV) and the newly emerging SARS-CoV-2. In this study, Next Generation Sequencing was used to gain new insights into cellular transcriptomic changes elicited by alphacoronavirus HCoV-229E. HCoV-229E-infected MRC5 cells showed marked downregulation of superpathway of cholesterol biosynthesis and eIF2 signaling pathways. Moreover, upregulation of cyclins, cell cycle control of chromosomal replication, and role of BRCA1 in DNA damage response, alongside downregulation of the cell cycle G1/S checkpoint, suggest that HCoV-229E favors S phase for viral infection. Intriguingly, more than 80% of key factors of cell innate immunity, interferon-stimulated genes (ISGs) and other transcripts of early antiviral response genes were downregulated early in HCoV-229E infection. This study will enhance our understanding of commonly circulating HCoVs and hopefully provide critical information about still-emerging coronaviruses.

2021-03-03 | GSE155986 | GEO

LC-MS/MS EThcD of MERS-CoV and SARS-CoV S N-linked glycopeptides from recombinant spike ectodomains and whole MERS virions

Project description:Recent outbreaks of severe acute respiratory syndrome and Middle-East respiratory syndrome along with the threat of a future coronavirus pandemic underscore the importance of finding ways to neutralize these viruses. The trimeric spike transmembrane glycoprotein S mediates entry into host cells and is the major target of neutralizing antibodies. To understand the humoral immune response elicited upon natural infections with coronaviruses, we structurally characterized the SARS-CoV and MERS-CoV S glycoproteins in complex with neutralizing antibodies isolated from human survivors using cryo electron microscopy and characterized the site-specific N-linked glycan profile of the recombinant S proteins with LC-MS/MS using EThcD fragmentation. Although the two antibodies studied blocked attachment to the host cell receptor, only the anti-SARS-CoV S antibody triggered premature fusogenic conformational changes via receptor functional mimicry. These results provide a structural framework for understanding coronavirus neutralization by human antibodies and shed light on the coronavirus fusion activation pathway which appears to take place through a receptor-driven ratcheting mechanism.

2019-05-01 | PXD010494 | Pride

Genome-scale identification of SARS-CoV-2 and pan-coronavirus host factor networks

Project description:The COVID-19 pandemic has claimed the lives of more than one million people worldwide. The causative agent, SARS-CoV-2, is a member of the Coronaviridae family, which are viruses that cause respiratory infections of varying severity. The cellular host factors and pathways co-opted by SARS- CoV-2 and other coronaviruses in the execution of their life cycles remain ill-defined. To develop an extensive compendium of host factors required for infection by SARS-CoV-2 and three seasonal coronaviruses (HCoV-OC43, HCoV-NL63, and HCoV-229E), we performed parallel genome-scale CRISPR knockout screens. These screens uncovered multiple host factors and pathways with pan- coronavirus and virus-specific functional roles, including major dependency on glycosaminoglycan biosynthesis, SREBP signaling, BMP signaling, and glycosylphosphatidylinositol biosynthesis, as well as a requirement for several poorly characterized proteins. We identified an absolute requirement for the VTT-domain containing protein TMEM41B for infection by SARS-CoV-2 and three seasonal coronaviruses. This human Coronaviridae host factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus spillover events.

2020-11-24 | GSE162038 | GEO

Longitudinal clonal IgG cross-reactivity profiles of coronavirus-specific B-cells in COVID-19 patients

Project description:We investigated the kinetics, breadth, magnitude, and level of cross-reactivity of IgG antibodies against SARS-CoV-2 and heterologous seasonal (HCoV-NL63, -229E, -OC43 and -HKU1) and epidemic coronaviruses (SARS-CoV, hCoV-MERS) at the clonal level in patients with mild or severe COVID-19 as well as in disease control patients. We assessed IgG antibody reactivity to nucleocapsid and spike antigens using protein microarray. A cutoff was set at the average plus 3 times the SD of 20 nonreactive cultures with a minimum MFI of 1000.

2022-09-30 | E-MTAB-12161 | biostudies-arrayexpress

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