The Role of TLR4 and CD14 Polymorphisms in the Pathogenesis of Respiratory Syncytial Virus Bronchiolitis in Greek Infants

Abstract

Clinical manifestations of respiratory syncytial virus (RSV) infection vary from minimal disease to severe acute bronchiolitis. The structural complex of TLR4/CD14 participates in the virus recognition as a component of natural immune response. Genetic variations of TLR4/CD14 may explain great variations in disease severity. The aim of this study was to investigate the possible role of polymorphisms of TLR4, Asp299Gly and Thr399Ile and CD14, C-159T and C-550T in the development of RSV bronchiolitis. Our study included two groups of Greek infants and young children (A and B). Group A consisted of 50 infants ≤2 years of age hospitalised with bronchiolitis and group B of 99 previously healthy children aged 4-14 years (control group) with a free past medical history. RSV was identified by PCR of genetic material that was extracted from nasopharyngeal samples collected from all patients. Blood samples were used to extract DNA and by using the PCR-RFLP method we performed TLR4 and CD14 genotyping. We found no association between TLR4 polymorphisms (Asp299Gly and Thr399Ile) and the development of acute bronchiolitis. For CD14 polymorphisms, a positive association was found between the C-159T and the development of bronchiolitis (p=0.05) but not for the other loci. There were no differences detected in the frequencies of the four polymorphisms studied among infants with RSV and non-RSV bronchiolitis. It is concluded that protein CD14 may have a functional role in the viral conjunction to the structural complex TLR4/CD14. The association between the polymorphism C-159T and the manifestation of disease found in our study points out that the severity in the development of acute bronchiolitis is not specified exclusively by the pathogen, but the immune response of the host also plays a significant role. More extensive multicentric studies need to take place, in order to lead to safer conclusions.

Genetic association of TLR4 Asp299Gly, TLR4 Thr399Ile, and CD14 C‐159T polymorphisms with the risk of severe RSV infection: a meta‐analysis

“…The main characteristics of all these studies are listed in Table . The genotype distributions of all 13 studies in the control groups conformed to the HWE except for one reported by Goutaki et al . (Table ).…”

“…In this meta‐analysis, a total of six studies involving 1009 cases and 1348 controls were included to investigate the association between TLR4 Asp299Gly polymorphism and the risk of severe RSV infection (as shown in Table ). The meta‐analysis showed no substantial heterogeneity among studies in five genetic models (I 2 < 50%); thus, the fixed‐effect model was used to calculate the pooled ORs of these models.…”

“…A meta‐analysis of the association between TLR4 Thr399Ile polymorphism and the risk of severe RSV infection included three studies with a total of 473 cases and 481 controls (as shown in Table ). Due to unobserved heterogeneity among these three studies (I 2 = 0%), the fixed‐effect model was used to calculate the pooled ORs in all genetic models.…”

Human Bocavirus 1 Infection: Clinical Cases

“…The diagnosis of HBoV1 not only could assist in the medical management of the patient but also contribute to surveillance of respiratory viruses, since the increased frequency of cases in the cold months ( Figure 1) accompanies the seasonal peak of other respiratory viruses such as RSV and FLU [45,46]. Recurrent episodes of LRTI might indicate a special susceptibility to respiratory infections and pathogens such as RSV or FLU can cause a severe illness depending on genetic risk factors that turn the host more vulnerable [47,48]. Therefore, patients with first-episode LRTI were compared to patients who had previous episodes of LRTI and hospitalization (Tables 1 and 2).…”

Disease severity in respiratory syncytial virus infection: Role of host genetic variation

“…Two nonsynonymous SNPs in the TLR4 gene (D299G and T399I) and −550C/T variation in the CD14 gene have been implicated with RSV infection due to their mediate on different responses to infection . Some studies supported a positive association between these SNPs and severe RSV bronchiolitis, while others could not replicate this association . However, in a meta‐analysis, Zhou et al reported that all of these polymorphisms are not associated with the risk of severe RSV infection .…”