Mannose-binding lectin in severe acute respiratory syndrome coronavirus infection.
Little is known about the innate immune response to severe acute respiratory syndrome (SARS) coronavirus (CoV) infection. Mannose-binding lectin (MBL), a key molecule in innate immunity, functions as an ante-antibody before the specific antibody response. Here, we describe a case-control study that included 569 patients with SARS and 1188 control subjects and used in vitro assays to investigate the role that MBL plays in SARS-CoV infection. The distribution of MBL gene polymorphisms was significantly different between patients with SARS and control subjects, with a higher frequency of haplotypes associated with low or deficient serum levels of MBL in patients with SARS than in control subjects. Serum levels of MBL were also significantly lower in patients with SARS than in control subjects. There was, however, no association between MBL genotypes, which are associated with low or deficient serum levels of MBL, and mortality related to SARS. MBL could bind SARS-CoV in a dose- and calcium-dependent and mannan-inhibitable fashion in vitro, suggesting that binding is through the carbohydrate recognition domains of MBL. Furthermore, deposition of complement C4 on SARS-CoV was enhanced by MBL. Inhibition of the infectivity of SARS-CoV by MBL in fetal rhesus kidney cells (FRhK-4) was also observed. These results suggest that MBL contributes to the first-line host defense against SARS-CoV and that MBL deficiency is a susceptibility factor for acquisition of SARS.
Ip
W K Eddie
WK
Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, China.
Chan
Kwok Hung
KH
Law
Helen K W
HK
Tso
Gloria H W
GH
Kong
Eric K P
EK
Wong
Wilfred H S
WH
To
Yuk Fai
YF
Yung
Raymond W H
RW
Chow
Eudora Y
EY
Au
Ka Leung
KL
Chan
Eric Y T
EY
Lim
Wilina
W
Jensenius
Jens C
JC
Turner
Malcolm W
MW
Peiris
J S Malik
JS
Lau
Yu Lung
YL
D000328:Adult; D003167:Complement Activation; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood* / Q000235:genetics*; D011485:Protein Binding; D045169:Severe Acute Respiratory Syndrome / Q000235:genetics* / Q000276:immunology*
D037601:Mannose-Binding Lectin