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Retroviruses pseudotyped with the severe acute respiratory syndrome coronavirus spike protein efficiently infect cells expressing angiotensin-converting enzyme 2

Academic Article
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Overview

authors

  • Moore, M. J.
  • Dorfman, T.
  • Li, W. H.
  • Wong, S. K.
  • Li, Yuxing
  • Kuhn, J. H.
  • Coderre, J.
  • Vasilieva, N.
  • Han, Z. C.
  • Greenough, T. C.
  • Farzan, Michael
  • Choe, Hyeryun

publication date

  • October 2004

journal

  • Journal of Virology  Journal

abstract

  • Infection of receptor-bearing cells by coronaviruses is mediated by their spike (S) proteins. The coronavirus (SARS-CoV) that causes severe acute respiratory syndrome (SARS) infects cells expressing the receptor angiotensin-converting enzyme 2 (ACE2). Here we show that codon optimization of the SARS-CoV S-protein gene substantially enhanced S-protein expression. We also found that two retroviruses, simian immunodeficiency virus (SIV) and murine leukemia virus, both expressing green fluorescent protein and pseudotyped with SARS-CoV S protein or S-protein variants, efficiently infected HEK293T cells stably expressing ACE2. Infection mediated by an S-protein variant whose cytoplasmic domain had been truncated and altered to include a fragment of the cytoplasmic tail of the human immunodeficiency virus type 1 envelope glycoprotein was, in both cases, substantially more efficient than that mediated by wild-type S protein. Using S-protein-pseudotyped SIV, we found that the enzymatic activity of ACE2 made no contribution to S-protein-mediated infection. Finally, we show that a soluble and catalytically inactive form of ACE2 potently blocked infection by S-protein-pseudotyped retrovirus and by SARS-CoV. These results permit studies of SARS-CoV entry inhibitors without the use of live virus and suggest a candidate therapy for SARS.

subject areas

  • Amino Acid Sequence
  • Animals
  • Carboxypeptidases
  • Cell Line
  • HIV-1
  • Humans
  • Leukemia Virus, Murine
  • Membrane Glycoproteins
  • Molecular Sequence Data
  • Peptidyl-Dipeptidase A
  • Receptors, Virus
  • SARS Virus
  • Simian Immunodeficiency Virus
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • Virion
  • Virus Replication
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Identity

PubMed Central ID

  • PMC516384

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.78.19.10628-10635.2004

PubMed ID

  • 15367630
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Additional Document Info

start page

  • 10628

end page

  • 10635

volume

  • 78

issue

  • 19

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