Variants of the chemokine receptor CCR5 are associated with severe bronchiolitis caused by respiratory syncytial virus.
Respiratory syncytial virus (RSV) bronchiolitis is characterized by intense inflammation of the airways, and high levels of proinflammatory cytokines and chemokines can be found in respiratory secretions of affected infants. Important among these chemokines are RANTES (regulated on activation, normal T cell-expressed and -secreted) and macrophage inflammatory-protein alpha, MIP-1alpha, both of which show correlation with severe RSV bronchiolitis. It is not clear whether high levels of these chemokines are important in disease pathogenesis, and this study addresses this question by studying genetic variants of their major receptor, CC chemokine receptor 5. Results from both a case-control and family-based genetic-association analysis show that the -2459G and -2554T variants are associated with severe RSV bronchiolitis (P=.01). It is proposed that these CCR5 variants influence the inflammatory response, and these data provide further evidence of the important role that host genetic variability plays in the determination of disease severity in RSV bronchiolitis.
Hull
Jeremy
J
University Department of Paediatrics, John Radcliffe Hospital, Headington, Oxford, UK. jhull@molbiol.ox.ac.uk
Rowlands
Kate
K
Lockhart
Elizabeth
E
Moore
Catrin
C
Sharland
Mike
M
Kwiatkowski
Dominic
D
D001990:Bronchiolitis, Viral / Q000235:genetics* / Q000503:physiopathology / Q000821:virology; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019713:Receptors, CCR5 / Q000235:genetics*; D018357:Respiratory Syncytial Virus Infections / Q000235:genetics* / Q000503:physiopathology / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000472:pathogenicity*; D012720:Severity of Illness Index
D019713:Receptors, CCR5