CCR5 deficiency predisposes to fatal outcome in influenza virus infection.
Influenza epidemics affect all age groups, although children, the elderly and those with underlying medical conditions are the most severely affected. Whereas co-morbidities are present in 50% of fatal cases, 25-50% of deaths are in apparently healthy individuals. This suggests underlying genetic determinants that govern infection severity. Although some viral factors that contribute to influenza disease are known, the role of host genetic factors remains undetermined. Data for small cohorts of influenza-infected patients are contradictory regarding the potential role of chemokine receptor 5 deficiency (CCR5-Δ32 mutation, a 32 bp deletion in the CCR5 gene) in the outcome of influenza virus infection. We tested 171 respiratory samples from influenza patients (2009 pandemic) for CCR5-Δ32 and evaluated its correlation with patient mortality. CCR5-Δ32 patients (17.4%) showed a higher mortality rate than WT individuals (4.7%; P = 0.021), which indicates that CCR5-Δ32 patients are at higher risk than the normal population of a fatal outcome in influenza infection.
Centro Nacional de Biotecnología, CSIC, Madrid, Spain.|CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III (CIBERES-ISCIII), Spain.
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Falcon
National Influenza Center, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
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Cuevas
Centro Nacional de Biotecnología, CSIC, Madrid, Spain.|CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III (CIBERES-ISCIII), Spain.
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Rodriguez-Frandsen
National Influenza Center, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
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Reyes
National Influenza Center, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
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Pozo
National Influenza Center, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
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Moreno
National Influenza Center, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
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Ledesma
Hospital General de Ciudad Real, Ciudad Real, Spain.
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Martínez-Alarcón
Centro Nacional de Biotecnología, CSIC, Madrid, Spain.|CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III (CIBERES-ISCIII), Spain.
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Nieto
National Influenza Center, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Madrid, Spain.
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Casas
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000502:physiology*; D007251:Influenza, Human / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000821:virology; D008297:Male; D008875:Middle Aged; D019713:Receptors, CCR5 / Q000172:deficiency* / Q000235:genetics; D055815:Young Adult
D019713:Receptors, CCR5