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PMID:15496474

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Citation

Jeffers, SA, Tusell, SM, Gillim-Ross, L, Hemmila, EM, Achenbach, JE, Babcock, GJ, Thomas, WD Jr, Thackray, LB, Young, MD, Mason, RJ, Ambrosino, DM, Wentworth, DE, Demartini, JC and Holmes, KV (2004) CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. Proc. Natl. Acad. Sci. U.S.A. 101:15748-53

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, S(590) and S(1180). 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.

Links

PubMed PMC524836 Online version:10.1073/pnas.0403812101

Keywords

Animals; Base Sequence; CHO Cells; Cell Cycle Proteins/genetics; Cell Cycle Proteins/physiology; Cell Line; Cricetinae; DNA, Complementary/genetics; Gene Library; Humans; Lung/metabolism; Lung/virology; Membrane Proteins/genetics; Membrane Proteins/physiology; Receptors, Virus/genetics; Receptors, Virus/physiology; Recombinant Proteins/genetics; Recombinant Proteins/metabolism; SARS Virus/pathogenicity; SARS Virus/physiology; Transduction, Genetic

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:CLC4M

enables

GO:0001618: virus receptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:CLC4M

enables

GO:0001618: virus receptor activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:CLC4M

GO:0001618: viral receptor activity

ECO:0000314:

F

Fig. 4

complete
CACAO 2299

HUMAN:CLC4M

GO:0001618: viral receptor activity

ECO:0000315:

F

Fig. 2A

complete
CACAO 2297


See also

References

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