CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus

Scott A. Jeffers, Sonia M. Tusell, Laura Gillim-Ross, Erin M. Hemmila, Jenna E. Achenbach, Gregory J. Babcock, William D. Thomas, Larissa B. Thackray, Mark D. Young, Robert J. Mason, Donna M. Ambrosino, David E. Wentworth, James C. DeMartini, Kathryn V. Holmes

Research output: Contribution to journalArticlepeer-review

425 Scopus citations

Abstract

Angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV, the novel coronavirus that causes severe acute respiratory syndrome [Li, W. Moore, M. J., Vasilieva, N., Sui, J., Wong, S. K., Berne, M. A., Somasundaran, M., Sullivan, J. L., Luzuriaga, K., Greenough, T. C., et al. (2003) Nature 426, 450-454]. We have identified a different human cellular glycoprotein that can serve as an alternative receptor for SARS-CoV. A human lung cDNA library in vesicular stomatitis virus G pseudotyped retrovirus was transduced into Chinese hamster ovary cells, and the cells were sorted for binding of soluble SARS-CoV spike (S) glycoproteins, S590 and S1180. Clones of transduced cells that bound SARS-CoV S glycoprotein were inoculated with SARS-CoV, and increases in subgenomic viral RNA from 1-16 h or more were detected by multiplex RT-PCR in four cloned cell lines. Sequencing of the human lung cDNA inserts showed that each of the cloned cell lines contained cDNA that encoded human CD209L, a C-type lectin (also called L-SIGN). When the cDNA encoding CD209L from clone 2.27 was cloned and transfected into Chinese hamster ovary cells, the cells expressed human CD209L glycoprotein and became susceptible to infection with SARS-CoV. Immunohistochemistry showed that CD209L is expressed in human lung in type II alveolar cells and endothelial cells, both potential targets for SARS-CoV. Several other enveloped viruses including Ebola and Sindbis also use CD209L as a portal of entry, and HIV and hepatitis C virus can bind to CD209L on cell membranes but do not use it to mediate virus entry. Our data suggest that the large S glycoprotein of SARS-CoV may use both ACE2 and CD209L in virus infection and pathogenesis.

Original languageEnglish
Pages (from-to)15748-15753
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number44
DOIs
StatePublished - Nov 2 2004

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