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

doi:10.1073/pnas.0403812101

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

^*Department of Microbiology and ^‡Molecular Biology Program, University Colorado Health Sciences Center, Denver, CO 80262; ^§Wadsworth Center, New York State Department of Health, Albany, NY 12202; ^¶Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523; ^∥Massachusetts Biologic Laboratories, University of Massachusetts Medical School, Jamaica Plain, MA 02130; ^**Department of Medicine, National Jewish Medical Research Center, Denver, CO 80206; and ^††Department of Biomedical Sciences, University of Albany, State University of New York, Albany, NY 12202

Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY (received for review May 28, 2004)

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.

Footnotes

↵ ‡‡ To whom correspondence should be addressed at: Department of Microbiology, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Campus Box B-175, Denver, CO 80262. E-mail: kathryn.holmes{at}uchsc.edu.
↵ † S.A.J. and S.M.T. contributed equally to this work.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: CHO, Chinese hamster ovary; CoV, coronavirus; FACS, fluorescence-activated cell sorting; moi, multiplicity of infection; MoMuLV, Moloney murine leukemia virus; PI, postinoculation; SARS, severe acute respiratory syndrome.