Association of TLR4 polymorphisms with symptomatic respiratory syncytial virus infection in high-risk infants and young children.

摘要: Respiratory syncytial virus (RSV) is a leading cause of infant mortality worldwide. Although anti-RSV Ab prophylaxis has greatly reduced in the United States, there currently no vaccine or effective antiviral therapy. RSV fusion (F) protein activates cells through TLR4. Two single nucleotide polymorphisms (SNPs) encoding Asp299Gly and Thr399Ile substitutions TLR4 ectodomain were previously associated with hyporesponsiveness increased susceptibility to bacterial infection. Prevalence these SNPs was analyzed case series 105 DNA samples extracted from archived nasal lavage high-risk infants/young children confirmed disease who participated two seminal clinical trials for prophylaxis. Frequencies compared those literature controls, healthy adults, infants, young presented symptoms respiratory infections (but not preselected high risk RSV). Both highly symptomatic this largely premature population (p < 0.0001), 89.5% 87.6% cases being heterozygous versus published control frequencies 10.5% 6.5%, respectively. The other groups had similarly low frequencies. Our data suggest that heterozygosity extracellular infants support dual role prematurity revealed by analysis either alone.