Homozygous L-SIGN (CLEC4M) plays a protective role in SARS coronavirus infection

Nat Genet. 2006 Jan;38(1):38-46. doi: 10.1038/ng1698. Epub 2005 Dec 20.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells / virology
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • Chlorocebus aethiops
  • Cohort Studies
  • Cricetinae
  • Cricetulus
  • Genetic Predisposition to Disease
  • Homozygote
  • Hong Kong / epidemiology
  • Humans
  • Intestine, Small / physiology
  • Lectins, C-Type / genetics*
  • Lectins, C-Type / metabolism
  • Lung / physiology
  • Lung / virology
  • Molecular Sequence Data
  • Proteasome Endopeptidase Complex / metabolism
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / metabolism
  • SARS Virus / metabolism
  • SARS Virus / pathogenicity*
  • Severe Acute Respiratory Syndrome / epidemiology
  • Severe Acute Respiratory Syndrome / genetics*
  • Tandem Repeat Sequences
  • Vero Cells / virology

Substances

  • CLEC4M protein, human
  • Cell Adhesion Molecules
  • Lectins, C-Type
  • Receptors, Cell Surface
  • Proteasome Endopeptidase Complex

Associated data

  • GENBANK/AB046569
  • GENBANK/AF290887