pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)5642-5650
Number of pages9
JournalJournal of Virology
Volume78
Issue number11
DOIs
StatePublished - Jun 2004
Externally publishedYes

Fingerprint

Severe Acute Respiratory Syndrome
Coronavirus
dendritic cells
Dendritic Cells
glycoproteins
Glycoproteins
Viruses
Tropism
cells
tropisms
Coronavirus Spike Glycoproteins
viruses
SARS Virus
Viral Envelope Proteins
Vero Cells
antiviral agents
Felidae
Myeloid Cells
Endocytosis
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN. / Yang, Zhi Yong; Huang, Yue; Ganesh, Lakshmanan; Leung, Kwanyee; Kong, Wing Pui; Schwartz, Owen; Subbarao, Kanta; Nabel, Gary J.

In: Journal of Virology, Vol. 78, No. 11, 06.2004, p. 5642-5650.

Research output: Contribution to journalArticle

Yang, Zhi Yong ; Huang, Yue ; Ganesh, Lakshmanan ; Leung, Kwanyee ; Kong, Wing Pui ; Schwartz, Owen ; Subbarao, Kanta ; Nabel, Gary J. / pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN. In: Journal of Virology. 2004 ; Vol. 78, No. 11. pp. 5642-5650.
@article{b7d898815bec41faba86c5a90986721c,
title = "pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN",
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.",
author = "Yang, {Zhi Yong} and Yue Huang and Lakshmanan Ganesh and Kwanyee Leung and Kong, {Wing Pui} and Owen Schwartz and Kanta Subbarao and Nabel, {Gary J.}",
year = "2004",
month = "6",
doi = "10.1128/JVI.78.11.5642-5650.2004",
language = "English (US)",
volume = "78",
pages = "5642--5650",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "11",

}

TY - JOUR

T1 - pH-dependent entry of severe acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer through DC-SIGN

AU - Yang, Zhi Yong

AU - Huang, Yue

AU - Ganesh, Lakshmanan

AU - Leung, Kwanyee

AU - Kong, Wing Pui

AU - Schwartz, Owen

AU - Subbarao, Kanta

AU - Nabel, Gary J.

PY - 2004/6

Y1 - 2004/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=2442691605&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2442691605&partnerID=8YFLogxK

U2 - 10.1128/JVI.78.11.5642-5650.2004

DO - 10.1128/JVI.78.11.5642-5650.2004

M3 - Article

VL - 78

SP - 5642

EP - 5650

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 11

ER -