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Lack of support for an association between CLEC4M homozygosity and protection against SARS coronavirus infection

Nature Genetics volume 39, pages 691–692 (2007)Cite this article

A Correspondence to this article was published on 01 June 2007

To the Editor:

Chan et al.1 reported that individuals homozygous for a tandem repeat polymorphism (VNTR) in exon 4 of CLEC4M were protected against SARS coronavirus infection (odds ratio of 0.7), whereas heterozygotes were more susceptible to infection. This repeat region encodes the extracellular neck domain of the L-SIGN ('liver/lymph node-specific ICAM-3 grabbing nonintegrin') molecule, which is responsible for oligomerization into a functional tetramer. Functional studies by Chan et al. suggested that the protective effect was due to formation of a homotetramer of L-SIGN, with apparently higher affinity for viral ligands, in homozygous subjects. However, the authors also indicated that a similar protective effect was observed in cells that expressed L-SIGN with only two repeats (see Supplementary Fig. 6 in Chan et al.). This finding is not consistent with the hypothesis that formation of homotetrameric L-SIGN accounts for protection against trans infection, because L-SIGN with two repeats cannot form stable tetramers2,3, and monomeric receptors show much lower affinity and avidity for viral ligands3. Furthermore, the presence of a variety of alternatively spliced CLEC4M mRNAs, including isoforms with partial deletion in the neck region, suggests that the correlation between genotype and function may not be a simple one4.

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Authors and Affiliations

  1. Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China

    Nelson Leung-Sang Tang & Yuk Ming Dennis Lo

  2. Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China

    Nelson Leung-Sang Tang & Yuk Ming Dennis Lo

  3. Department of Microbiology, The Chinese University of Hong Kong, Hong Kong, People's Republic of China

    Paul Kay-Sheung Chan

  4. Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, People's Republic of China

    David Shu-Cheong Hui, Francis K L Chan & Joseph Jao-Yiu Sung

  5. Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, People's Republic of China

    David Shu-Cheong Hui & Joseph Jao-Yiu Sung

  6. Department of Anatomical and Cellular Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, People's Republic of China

    Ka-Fai To

  7. Peking Union Medical College Hospital, Beijing, People's Republic of China

    Weimin Zhang

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  1. Nelson Leung-Sang Tang
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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Comparison of genotype distributions and homozygote proportions between SARS patients with different prognoses. (PDF 34 kb)

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Tang, NS., Chan, PS., Hui, DC. et al. Lack of support for an association between CLEC4M homozygosity and protection against SARS coronavirus infection. Nat Genet 39, 691–692 (2007). https://doi.org/10.1038/ng0607-691

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