<i>TLR</i>‐4 and <i>CD</i>14 Polymorphisms in Respiratory Syncytial Virus Associated Disease

Puthothu, Beena; Förster, Johannes; Heinzmann, Andrea; Krueger, Marcus

doi:10.1155/2006/865890

Cited by 72 publications

(72 citation statements)

References 27 publications

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“…To determine whether CD14 affected RSV disease severity, we asked whether the CD14 C-159T and CD14 C-550T SNPs were also associated with RSV bronchiolitis (Figure 1, F and G, and Supplemental Table 8). Allelic frequencies for both SNPs were in Hardy-Weinberg equilibrium and did not differ from those reported previously (16,17,31). Unlike TLR4 Asp299Gly, CD14 C-159T and CD14 C-550T did not affect RSV disease severity.…”

Section: Introductionsupporting

confidence: 64%

“…Control subjects included infants with oxygen saturation at or above 93% while breathing room air. In addition, these criteria allow comparison with numerous previous studies (15)(16)(17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

“…Environmental exposure (15,19), lack of power (17)(18)(19), choice of controls (15)(16)(17)(18)(19), or specific genetic or demographic characteristics of the population (16) may explain the differences between human studies. In fact, our observations and those of others (47) suggest that the effect of TLR4 in disease severity does not occur through interaction of this PRR with the virus but rather through prior environmental TLR4 activation conditioning the immune response to infection.…”

Section: Discussionmentioning

confidence: 99%

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TLR4 genotype and environmental LPS mediate RSV bronchiolitis through Th2 polarization

Caballero¹,

Serra²,

Acosta³

et al. 2015

J. Clin. Invest.

110

128

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Section: Introductionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

TLR4 genotype and environmental LPS mediate RSV bronchiolitis through Th2 polarization

Caballero¹,

Serra²,

Acosta³

et al. 2015

J. Clin. Invest.

110

128

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“…More recently, studies have provided evidence associating increased incidence of severe pediatric RSV disease with genetic polymorphisms in a number of genes selected for analysis, although these studies seem preliminary and sometimes are inconsistent. These associations include genes encoding cytokines and chemokines, including interleukin-4 (IL-4), IL-8/CXCL8, IL-10, IL-13, and RANTES/CCL5, or encoding proteins involved in surface interactions or intracellular signaling, such as TLR4, CD14, IL-4R, CX3CR1, CCR5, and surfactant protein A (SP-A), SP-B, SP-C, and SP-D (4,6,69,71,115,(125)(126)(127)144). Some of these polymorphisms have been associated with functional effects that give clues to possible beneficial or pathological roles of host factors in RSV infection, some of which are noted below.…”

Section: Host Risk Factorsmentioning

confidence: 99%

“…Silencing the TLR4 gene in mice appeared to have no discernible effect on viral replication, disease, or the host response during infection with RSV or with its murine counterpart PVM (33,37). In humans, several studies have investigated a possible link between pediatric RSV disease and two coding polymorphisms in TLR4 that are associated with TLR4 hyporesponsiveness and increased susceptibility to bacterial infection (6,115,126,144). Tal et al found that these two polymorphisms indeed were associated more frequently with RSV bronchiolitis than with controls (144), consistent with a protective role for TLR4.…”

Section: Rsv Is Not Highly Cytopathic or Invasivementioning

confidence: 99%

Viral and Host Factors in Human Respiratory Syncytial Virus Pathogenesis

Collins¹,

Graham

2008

J Virol

427

478

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Human respiratory syncytial virus (RSV) was first isolated in 1956 from a laboratory chimpanzee with upper respiratory tract disease (for general reviews, see references 21, 57, 102, and 145). RSV was quickly determined to be of human origin and was shown to be the leading worldwide viral agent of serious pediatric respiratory tract disease. In a 13-year prospective study of infants and children in the United States, RSV was detected in 43%, 25%, 11%, and 10% of pediatric hospitalizations for bronchiolitis, pneumonia, bronchitis, and croup, respectively (110). Approximately two-thirds of infants are infected with RSV during the first year of life, and 90% have been infected one or more times by 2 years of age. The rate of hospitalization for primary infection is approximately 0.5% but can vary by situation and ethnic group and can be as high as 25% (77).RSV also is a significant cause of morbidity and mortality in the elderly, with an impact approaching that of nonpandemic influenza virus (39). RSV readily infects severely immunocompromised individuals, most notably allogeneic bone marrow transplant recipients, causing high mortality. RSV also makes a substantial contribution to upper respiratory tract disease in individuals of all ages (59,65 Although RSV has a single serotype, reinfection can occur throughout life. RSV in yearly winter/early spring epidemics in temperate regions; elsewhere, the timing of RSV activity can vary widely with the locale. The RSV reservoir in the offseason is unknown. Strains circulate quickly around the earth (150). Neither a vaccine nor an effective antiviral therapy is available, although there is active research in both areas (23,78,138). However, infants at high risk for serious disease can receive passive immunoprophylaxis during the epidemic season by a monthly injection of a commercial RSV-neutralizing monoclonal antibody, palivizumab (Synagis), which provides a 55% reduction in RSV-associated hospitalization (17). THE VIRUSRSV (family Paramyxoviridae, order Mononegavirales) is an enveloped virus with a single-stranded negative-sense RNA genome of 15.2 kb (21). There are animal versions of RSV, including bovine RSV (BRSV) and pneumonia virus of mice (PVM), suggesting that species jumping occurred during the evolution of these viruses. However, there is no animal reservoir for human RSV.Efficient infection by RSV of established cell lines in vitro involves binding to cell-surface glycosaminoglycans (62). However, it is not known how closely this binding models attachment in vivo or whether it is an initial interaction that is followed by a second, higher-affinity step that remains to be identified. The nucleocapsid gains entry to the cytoplasm by membrane fusion; surprisingly, this may involve clathrin-mediated endocytosis rather than surface fusion typical of paramyxoviruses (85). Viral gene expression and RNA replication occur in the cytoplasm, and virions acquire a lipid envelope by budding through the plasmid membrane (Fig. 1). Virions are pleomorphic and include spheres ...

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Confirmation of an association between single nucleotide polymorphisms in the VDR gene with respiratory syncytial virus related disease in South African Children

Kresfelder

Janssen

Bont

et al. 2011

Journal of Medical Virology

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Respiratory syncytial virus is a leading cause of lower respiratory tract infection in infants. Disease severity has been linked to host immune responses and polymorphisms in genes associated with innate immunity. A large‐scale genetics study of single nucleotide polymorphisms (SNPs) in children in the Netherlands identified SNPs in the vitamin D receptor (VDR) and JUN genes which have a strong association with an increased risk of developing bronchiolitis following the first respiratory syncytial virus (RSV) infection. The Toll‐like receptor 4 (TLR4) gene has two SNPs which have been associated previously with RSV disease severity in various populations. The aim of this study was to determine if these SNPs may be associated with RSV disease in African children in South Africa. RSV patient (n = 296) and control (n = 113) groups were established (median ages: 3 and 3.5 months) and DNA extracted from the collected specimens. Real‐time polymerase chain reaction using hydrolysis probes was used to screen for SNPs in the VDR (Thr1Meth; rs10735810), TLR4 (Asp299Gly; rs4986790 and Thr399Ile; rs4986791) and JUN (c.750G/A; rs11688) genes. Carriers of the VDR (Thr1Meth) SNP minor T allele were more prone to RSV disease than individuals in the control group. The TLR4 (Asp299Gly), TLR4 (Thr399Ile), and JUN (c.750G/A) SNPs showed no significant association with RSV disease. It is concluded that children carrying the minor T allele of the VDR (Thr1Meth) SNP may be predisposed to RSV disease, as this SNP was identified as a risk factor for severe RSV disease in South African children, confirming the findings in the Netherlands. J. Med. Virol. 83:1834–1840, 2011. © 2011 Wiley‐Liss, Inc.

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TLR‐4 and CD14 Polymorphisms in Respiratory Syncytial Virus Associated Disease

Cited by 72 publications

References 27 publications

TLR4 genotype and environmental LPS mediate RSV bronchiolitis through Th2 polarization

TLR4 genotype and environmental LPS mediate RSV bronchiolitis through Th2 polarization

Viral and Host Factors in Human Respiratory Syncytial Virus Pathogenesis

Confirmation of an association between single nucleotide polymorphisms in the VDR gene with respiratory syncytial virus related disease in South African Children

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