T280M variation of the CX3C receptor gene is associated with increased risk for severe respiratory syncytial virus bronchiolitis.
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.
Amanatidou
Virginia
V
Laboratory of Clinical Virology, Medical School, University of Crete, Greece.
Sourvinos
George
G
Apostolakis
Stavros
S
Tsilimigaki
Amalia
A
Spandidos
Demetrios A
DA
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
D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; D008565:Membrane Proteins; D018121:Receptors, Cytokine; D015728:Receptors, HIV