Homozygous L-SIGN (CLEC4M) plays a protective role in SARS coronavirus infection.
Severe acute respiratory syndrome (SARS) is caused by infection of a previously undescribed coronavirus (CoV). L-SIGN, encoded by CLEC4M (also known as CD209L), is a SARS-CoV binding receptor that has polymorphism in its extracellular neck region encoded by the tandem repeat domain in exon 4. Our genetic risk association study shows that individuals homozygous for CLEC4M tandem repeats are less susceptible to SARS infection. L-SIGN is expressed in both non-SARS and SARS-CoV-infected lung. Compared with cells heterozygous for L-SIGN, cells homozygous for L-SIGN show higher binding capacity for SARS-CoV, higher proteasome-dependent viral degradation and a lower capacity for trans infection. Thus, homozygosity for L-SIGN plays a protective role during SARS infection.
Chan
Vera S F
VS
Department of Surgery, Hong Kong Jockey Club Clinical Research Center, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, SAR, China.
Chan
Kelvin Y K
KY
Chen
Yongxiong
Y
Poon
Leo L M
LL
Cheung
Annie N Y
AN
Zheng
Bojian
B
Chan
Kwok-Hung
KH
Mak
William
W
Ngan
Hextan Y S
HY
Xu
Xiaoning
X
Screaton
Gavin
G
Tam
Paul K H
PK
Austyn
Jonathan M
JM
Chan
Li-Chong
LC
Yip
Shea-Ping
SP
Peiris
Malik
M
Khoo
Ui-Soon
US
Lin
Chen-Lung S
CL
D000818:Animals; D016466:CHO Cells / Q000821:virology; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002522:Chlorocebus aethiops; D015331:Cohort Studies; D006224:Cricetinae; D003412:Cricetulus; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D007421:Intestine, Small / Q000502:physiology; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000502:physiology / Q000821:virology; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism / Q000472:pathogenicity*; D045169:Severe Acute Respiratory Syndrome / Q000453:epidemiology / Q000235:genetics*; D020080:Tandem Repeat Sequences; D014709:Vero Cells / Q000821:virology
C433029:CLEC4M protein, human; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D046988:Proteasome Endopeptidase Complex