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Retroviruses pseudotyped with the severe acute respiratory syndrome coronavirus spike protein efficiently infect cells expressing angiotensin-converting enzyme 2.
J Virol. 2004 Oct; 78(19):10628-35.JV

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.

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Authors+Show Affiliations

Moore MJ
Partners AIDS Research Center, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, MA, USA.
Dorfman T
No affiliation info available
Li W
No affiliation info available
Wong SK
No affiliation info available
Li Y
No affiliation info available
Kuhn JH
No affiliation info available
Coderre J
No affiliation info available
Vasilieva N
No affiliation info available
Han Z
No affiliation info available
Greenough TC
No affiliation info available
Farzan M
No affiliation info available
Choe H
No affiliation info available

MeSH

Amino Acid SequenceAngiotensin-Converting Enzyme 2AnimalsCarboxypeptidasesCell LineHIV-1HumansLeukemia Virus, MurineMembrane GlycoproteinsMolecular Sequence DataPeptidyl-Dipeptidase AReceptors, VirusSevere acute respiratory syndrome-related coronavirusSimian Immunodeficiency VirusSpike Glycoprotein, CoronavirusViral Envelope ProteinsVirionVirus Replication

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15367630

Citation

Moore, Michael J., et al. "Retroviruses Pseudotyped With the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Efficiently Infect Cells Expressing Angiotensin-converting Enzyme 2." Journal of Virology, vol. 78, no. 19, 2004, pp. 10628-35.
Moore MJ, Dorfman T, Li W, et al. Retroviruses pseudotyped with the severe acute respiratory syndrome coronavirus spike protein efficiently infect cells expressing angiotensin-converting enzyme 2. J Virol. 2004;78(19):10628-35.
Moore, M. J., Dorfman, T., Li, W., Wong, S. K., Li, Y., Kuhn, J. H., Coderre, J., Vasilieva, N., Han, Z., Greenough, T. C., Farzan, M., & Choe, H. (2004). Retroviruses pseudotyped with the severe acute respiratory syndrome coronavirus spike protein efficiently infect cells expressing angiotensin-converting enzyme 2. Journal of Virology, 78(19), 10628-35.
Moore MJ, et al. Retroviruses Pseudotyped With the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Efficiently Infect Cells Expressing Angiotensin-converting Enzyme 2. J Virol. 2004;78(19):10628-35. PubMed PMID: 15367630.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Retroviruses pseudotyped with the severe acute respiratory syndrome coronavirus spike protein efficiently infect cells expressing angiotensin-converting enzyme 2. AU - Moore,Michael J, AU - Dorfman,Tatyana, AU - Li,Wenhui, AU - Wong,Swee Kee, AU - Li,Yanhan, AU - Kuhn,Jens H, AU - Coderre,James, AU - Vasilieva,Natalya, AU - Han,Zhongchao, AU - Greenough,Thomas C, AU - Farzan,Michael, AU - Choe,Hyeryun, PY - 2004/9/16/pubmed PY - 2004/10/22/medline PY - 2004/9/16/entrez SP - 10628 EP - 35 JF - Journal of virology JO - J Virol VL - 78 IS - 19 N2 - 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. SN - 0022-538X UR - https://www.unboundmedicine.com/medline/citation/15367630/Retroviruses_pseudotyped_with_the_severe_acute_respiratory_syndrome_coronavirus_spike_protein_efficiently_infect_cells_expressing_angiotensin_converting_enzyme_2_ DB - PRIME DP - Unbound Medicine ER -