title: T280M variation of the CX3C receptor gene is associated with increased risk for severe respiratory syncytial virus bronchiolitis.
abstract: BACKGROUND
  Recent data suggest that immunologic response during respiratory syncytial virus (RSV) infection is partially modified through interaction of viral G glycoprotein with the host's chemokine receptor, CX3CR1. We hypothesized that two nonsynonymous, single-nucleotide polymorphisms of the CX3CR1 gene (CX3CR1-V249I and CX3CR1-T280M) that disrupt the affinity of CX3CR1 for its natural ligand (fractalkine) could also affect the G glycoprotein-CX3CR1 pathway.
  
  
  METHODS
  To test the hypothesis, DNA samples were obtained from 82 children hospitalized for RSV bronchiolitis in a 1-year period. One hundred twenty sex-matched healthy adults, without a history of severe lower respiratory tract infections, formed the control group.
  
  
  RESULTS
  Epidemiologic data showed an increase in the RSV infection rate during the late winter season, with a peak rate in early spring. Genotyping revealed predominance of the 280M-containing genotypes (M/M or T/M) in cases compared with controls (37.8% versus 20.8%, respectively; odds ratio, 2.03; 95% confidence interval, 1.1-3.9; P = 0.025), demonstrating an association between the common CX3CR1-T280M variations and increased risk of severe RSV bronchiolitis.
  
  
  CONCLUSIONS
  Our findings support the hypothesis of the pivotal role of the G glycoprotein CX3CR1 pathway in the pathogenesis of RSV bronchiolitis and propose CX3CR1 as a potential therapeutic target.
authors.affiliation: Laboratory of Clinical Virology, Medical School, University of Crete, Greece.
authors.forename: Virginia
authors.initials: V
authors.lastname: Amanatidou
authors.forename: George
authors.initials: G
authors.lastname: Sourvinos
authors.forename: Stavros
authors.initials: S
authors.lastname: Apostolakis
authors.forename: Amalia
authors.initials: A
authors.lastname: Tsilimigaki
authors.forename: Demetrios A
authors.initials: DA
authors.lastname: Spandidos
mesh_terms: D001990:Bronchiolitis, Viral / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology* / Q000821:virology; D000073883:CX3C Chemokine Receptor 1; D016022:Case-Control Studies; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D018121:Receptors, Cytokine / Q000235:genetics* / Q000378:metabolism; D015728:Receptors, HIV / Q000235:genetics* / Q000378:metabolism; D018357:Respiratory Syncytial Virus Infections / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000378:metabolism / Q000472:pathogenicity*; D012307:Risk Factors; D012621:Seasons; D012720:Severity of Illness Index
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D018121:Receptors, Cytokine; D015728:Receptors, HIV