CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus.
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.
Jeffers
Scott A
SA
Department of Microbiology and Molecular Biology Program, University Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA.
Tusell
Sonia M
SM
Gillim-Ross
Laura
L
Hemmila
Erin M
EM
Achenbach
Jenna E
JE
Babcock
Gregory J
GJ
Thomas
William D
WD
Thackray
Larissa B
LB
Young
Mark D
MD
Mason
Robert J
RJ
Ambrosino
Donna M
DM
Wentworth
David E
DE
Demartini
James C
JC
Holmes
Kathryn V
KV
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D015723:Gene Library; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000821:virology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D000085064:Receptors, Coronavirus; D011991:Receptors, Virus / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000472:pathogenicity* / Q000502:physiology; D014161:Transduction, Genetic
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; C089821:MS4A3 protein, human; D008565:Membrane Proteins; D000085064:Receptors, Coronavirus; D011991:Receptors, Virus; D011994:Recombinant Proteins