Association between common Toll-like receptor 4 mutations and severe respiratory syncytial virus disease

J Infect Dis. 2004 Jun 1;189(11):2057-63. doi: 10.1086/420830. Epub 2004 May 12.


Background: The clinical spectrum of respiratory syncytial virus (RSV) bronchiolitis in previously healthy infants is extremely variable. Thus, it is likely that factors such as genetic heterogeneity contribute to disease severity. Toll-like receptor 4 (TLR4) and CD14 are part of a receptor complex involved in the innate immune response to RSV.

Methods: The association of the TLR4 mutations (Asp299Gly and Thr399Ile) and the CD14/-159 polymorphism were analyzed in 99 infants hospitalized with severe RSV bronchiolitis (group I). Eighty-two ambulatory infants with mild RSV bronchiolitis (group II) and 90 healthy adults (group III) composed the 2 control groups. The TLR4 mutations and the CD14/-159 polymorphism were genotyped by use of reverse-transcriptase polymerase chain reaction and restriction fragment-length polymorphism analysis, respectively.

Results: Each of the TLR4 mutations, either alone or in cosegregation, were associated with severe RSV bronchiolitis: the Asp299Gly and Thr399Ile mutations were significantly overrepresented in group I, compared with groups II and III. No association between the CD14/-159 polymorphism and RSV bronchiolitis was found.

Conclusions: These findings suggest that TLR4 mutations, but not the CD14/-159 polymorphism, are associated with an increased risk of severe RSV bronchiolitis in previously healthy infants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bronchiolitis / immunology*
  • Bronchiolitis / pathology
  • Bronchiolitis / virology
  • Female
  • Genetic Variation
  • Humans
  • Infant
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharide Receptors / immunology
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / immunology*
  • Middle Aged
  • Point Mutation / genetics
  • Point Mutation / immunology
  • Polymorphism, Restriction Fragment Length
  • Prospective Studies
  • RNA, Viral / chemistry
  • RNA, Viral / genetics
  • Receptors, Cell Surface / genetics*
  • Receptors, Cell Surface / immunology*
  • Respiratory Syncytial Virus Infections / genetics*
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Viruses / genetics
  • Respiratory Syncytial Viruses / immunology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 4
  • Toll-Like Receptors


  • Lipopolysaccharide Receptors
  • Membrane Glycoproteins
  • RNA, Viral
  • Receptors, Cell Surface
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Toll-Like Receptors