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Pediatric Infectious Disease Journal:
doi: 10.1097/01.inf.0000214998.16248.b7
Original Studies

T280M Variation of the CX3C Receptor Gene Is Associated With Increased Risk for Severe Respiratory Syncytial Virus Bronchiolitis

Amanatidou, Virginia MD*; Sourvinos, George PhD*; Apostolakis, Stavros MD*; Tsilimigaki, Amalia MD†; Spandidos, Demetrios A. PhD*

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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.

© 2006 Lippincott Williams & Wilkins, Inc.

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