SrasV1, Ncbi, Curation, bibRecord, 000807

pH-Dependent Entry of Severe Acute Respiratory Syndrome Coronavirus Is Mediated by the Spike Glycoprotein and Enhanced by Dendritic Cell Transfer through DC-SIGN

Identifieur interne : 000807 ( Ncbi/Curation ); précédent : 000806; suivant : 000808

pH-Dependent Entry of Severe Acute Respiratory Syndrome Coronavirus Is Mediated by the Spike Glycoprotein and Enhanced by Dendritic Cell Transfer through DC-SIGN

Auteurs : Zhi-Yong Yang ; Yue Huang ; Lakshmanan Ganesh ; Kwanyee Leung ; Wing-Pui Kong ; Owen Schwartz ; Kanta Subbarao ; Gary J. Nabel

Source :

Journal of Virology [ 0022-538X ] ; 2004.

RBID : PMC:415834

Descripteurs français

English descriptors

KwdEn :
- Animals, Cell Adhesion Molecules (physiology), Cell Line, Dendritic Cells (physiology), Humans, Hydrogen-Ion Concentration, Lectins, C-Type (physiology), Membrane Glycoproteins (physiology), Receptors, Cell Surface (physiology), SARS Virus (physiology), Spike Glycoprotein, Coronavirus, Viral Envelope Proteins (physiology).
MESH :
- chemical , physiology : Cell Adhesion Molecules, Lectins, C-Type, Membrane Glycoproteins, Receptors, Cell Surface, Viral Envelope Proteins.
- physiology : Dendritic Cells, SARS Virus.
- Animals, Cell Line, Humans, Hydrogen-Ion Concentration, Spike Glycoprotein, Coronavirus.

Abstract

The severe acute respiratory syndrome coronavirus (SARS-CoV) synthesizes several putative viral envelope proteins, including the spike (S), membrane (M), and small envelope (E) glycoproteins. Although these proteins likely are essential for viral replication, their specific roles in SARS-CoV entry have not been defined. In this report, we show that the SARS-CoV S glycoprotein mediates viral entry through pH-dependent endocytosis. Further, we define its cellular tropism and demonstrate that virus transmission occurs through cell-mediated transfer by dendritic cells. The S glycoprotein was used successfully to pseudotype replication-defective retroviral and lentiviral vectors that readily infected Vero cells as well as primary pulmonary and renal epithelial cells from human, nonhuman primate, and, to a lesser extent, feline species. The tropism of this reporter virus was similar to that of wild-type, replication-competent SARS-CoV, and binding of purified S to susceptible target cells was demonstrated by flow cytometry. Although myeloid dendritic cells were able to interact with S and to bind virus, these cells could not be infected by SARS-CoV. However, these cells were able to transfer the virus to susceptible target cells through a synapse-like structure. Both cell-mediated infection and direct infection were inhibited by anti-S antisera, indicating that strategies directed toward this gene product are likely to confer a therapeutic benefit for antiviral drugs or the development of a SARS vaccine.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC415834

DOI: 10.1128/JVI.78.11.5642-5650.2004
PubMed: 15140961
PubMed Central: 415834

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PMC:415834

Le document en format XML

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<front><div type="abstract" xml:lang="en"><p>The severe acute respiratory syndrome coronavirus (SARS-CoV) synthesizes several putative viral envelope proteins, including the spike (S), membrane (M), and small envelope (E) glycoproteins. Although these proteins likely are essential for viral replication, their specific roles in SARS-CoV entry have not been defined. In this report, we show that the SARS-CoV S glycoprotein mediates viral entry through pH-dependent endocytosis. Further, we define its cellular tropism and demonstrate that virus transmission occurs through cell-mediated transfer by dendritic cells. The S glycoprotein was used successfully to pseudotype replication-defective retroviral and lentiviral vectors that readily infected Vero cells as well as primary pulmonary and renal epithelial cells from human, nonhuman primate, and, to a lesser extent, feline species. The tropism of this reporter virus was similar to that of wild-type, replication-competent SARS-CoV, and binding of purified S to susceptible target cells was demonstrated by flow cytometry. Although myeloid dendritic cells were able to interact with S and to bind virus, these cells could not be infected by SARS-CoV. However, these cells were able to transfer the virus to susceptible target cells through a synapse-like structure. Both cell-mediated infection and direct infection were inhibited by anti-S antisera, indicating that strategies directed toward this gene product are likely to confer a therapeutic benefit for antiviral drugs or the development of a SARS vaccine.</p>
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pH-Dependent Entry of Severe Acute Respiratory Syndrome Coronavirus Is Mediated by the Spike Glycoprotein and Enhanced by Dendritic Cell Transfer through DC-SIGN

pH-Dependent Entry of Severe Acute Respiratory Syndrome Coronavirus Is Mediated by the Spike Glycoprotein and Enhanced by Dendritic Cell Transfer through DC-SIGN

Source :

Descripteurs français

English descriptors

Abstract

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Links to Exploration step

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