Retroviruses Pseudotyped with the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Efficiently Infect Cells Expressing Angiotensin-Converting Enzyme 2
| Autor: | Wenhui Li, Swee Kee Wong, Natalya Vasilieva, Jens H. Kuhn, Tatyana Dorfman, Hyeryun Choe, Michael Farzan, Thomas C. Greenough, Zhongchao Han, Yanhan Li, James A. Coderre, Michael Moore |
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| Rok vydání: | 2004 |
| Předmět: |
viruses
Molecular Sequence Data Immunology Carboxypeptidases Peptidyl-Dipeptidase A Virus Replication medicine.disease_cause Microbiology Virus Cell Line Retrovirus Viral Envelope Proteins Nidovirales Virology Murine leukemia virus medicine Animals Humans Coronaviridae Amino Acid Sequence skin and connective tissue diseases Coronavirus Membrane Glycoproteins biology fungi Virion virus diseases Simian immunodeficiency virus biology.organism_classification Virus-Cell Interactions Leukemia Virus Murine Severe acute respiratory syndrome-related coronavirus Viral replication Insect Science Spike Glycoprotein Coronavirus HIV-1 Receptors Virus Simian Immunodeficiency Virus Angiotensin-Converting Enzyme 2 |
| Zdroj: | Journal of Virology |
| ISSN: | 0022-538X |
| DOI: | 10.1128/jvi.78.19.10628-10635.2004 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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