SrasV1, PubMed, Checkpoint, bibRecord, 001864

Identification of a new region of SARS-CoV S protein critical for viral entry.

Identifieur interne : 001864 ( PubMed/Checkpoint ); précédent : 001863; suivant : 001865

Identification of a new region of SARS-CoV S protein critical for viral entry.

Auteurs : Ying Guo [États-Unis] ; Jennifer Tisoncik ; Susanna Mcreynolds ; Michael Farzan ; Bellur S. Prabhakar ; Thomas Gallagher ; Lijun Rong ; Michael Caffrey

Source :

Journal of molecular biology [ 1089-8638 ] ; 2009.

RBID : pubmed:19853613

Descripteurs français

English descriptors

KwdEn :
- Amino Acid Substitution (genetics), Antiviral Agents (pharmacology), Cell Line, HIV (genetics), Host-Pathogen Interactions (drug effects), Humans, Inhibitory Concentration 50, Membrane Glycoproteins (genetics), Membrane Glycoproteins (metabolism), Mutagenesis, Site-Directed, Peptides (pharmacology), Peptidyl-Dipeptidase A (metabolism), Receptors, Virus (metabolism), SARS Virus (physiology), Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (genetics), Viral Envelope Proteins (metabolism), Virus Internalization.
MESH :
- chemical , genetics : Membrane Glycoproteins, Viral Envelope Proteins.
- chemical , metabolism : Membrane Glycoproteins, Peptidyl-Dipeptidase A, Receptors, Virus, Viral Envelope Proteins.
- chemical , pharmacology : Antiviral Agents, Peptides.
- drug effects : Host-Pathogen Interactions.
- genetics : Amino Acid Substitution, HIV.
- physiology : SARS Virus.
- Cell Line, Humans, Inhibitory Concentration 50, Mutagenesis, Site-Directed, Spike Glycoprotein, Coronavirus, Virus Internalization.

Abstract

Infection by severe acute respiratory syndrome coronavirus (SARS-CoV) is initiated by specific interactions between the SARS-CoV spike (S) protein and its receptor ACE2. In this report, we screened a peptide library representing the SARS-CoV S protein sequence using a human immunodeficiency virus-based pseudotyping system to identify specific regions that affect viral entry. One of the 169 peptides screened, peptide 9626 (S residues 217-234), inhibited SARS-CoV S-mediated entry of the pseudotyped virions in 293T cells expressing a functional SARS-CoV receptor (human angiotensin-converting enzyme 2) in a dose-dependent manner (IC(50) approximately 11 microM). Alanine scanning mutagenesis was performed to assess the roles of individual residues within this region of S, which was previously uncharacterized. The effects included significant reductions in expression (K223A), viral incorporation (L218A, I230A, and N232A), and reduced viral entry (L224A, L226A, I228A, T231A, and F233A). Taken together, these results reveal a new region of the S protein that is crucial for SARS-CoV entry.

DOI: 10.1016/j.jmb.2009.10.032
PubMed: 19853613

Affiliations:

Links toward previous steps (curation, corpus...)

to stream PubMed, to step Corpus: 001809
to stream PubMed, to step Curation: 001809

Links to Exploration step

pubmed:19853613

Le document en format XML

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<front><div type="abstract" xml:lang="en">Infection by severe acute respiratory syndrome coronavirus (SARS-CoV) is initiated by specific interactions between the SARS-CoV spike (S) protein and its receptor ACE2. In this report, we screened a peptide library representing the SARS-CoV S protein sequence using a human immunodeficiency virus-based pseudotyping system to identify specific regions that affect viral entry. One of the 169 peptides screened, peptide 9626 (S residues 217-234), inhibited SARS-CoV S-mediated entry of the pseudotyped virions in 293T cells expressing a functional SARS-CoV receptor (human angiotensin-converting enzyme 2) in a dose-dependent manner (IC(50) approximately 11 microM). Alanine scanning mutagenesis was performed to assess the roles of individual residues within this region of S, which was previously uncharacterized. The effects included significant reductions in expression (K223A), viral incorporation (L218A, I230A, and N232A), and reduced viral entry (L224A, L226A, I228A, T231A, and F233A). Taken together, these results reveal a new region of the S protein that is crucial for SARS-CoV entry.</div>
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Identification of a new region of SARS-CoV S protein critical for viral entry.

Identification of a new region of SARS-CoV S protein critical for viral entry.

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