A haplotype of the human CXCR1 gene protective against rapid disease progression in HIV-1<sup>+</sup>patients

Vasilescu, Alexandre; Terashima, Yuya; Enomoto, Mitsuhiro; Heath, SimonC.; Poonpiriya, Vongsakorn; Gatanaga, Hiroyuki; Do, Hervé; Diop, Gora; Hirtzig, Thomas; Auewarakul, Prasert; Lauhakirti, Darat; Sura, Thanyachai; Charneau, Pierre; Marullo, Stéfano; Therwath, Amu; Oka, Shomi; Kanegasaki, Shiro; Lathrop, Mark; Matsushima, Kouji; Zagury, Jean‐François; Matsuda, Fumihiko

doi:10.1073/pnas.0611670104

Cited by 26 publications

(28 citation statements)

References 31 publications

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“…Interestingly, we observed that minor allele frequencies of the majority of CXCR2 SNPs were higher compared with CXCR1 SNPs (table 1). Similar MAF distributions of CXCR1 and CXCR2 SNPs have been demonstrated previously in a control cohort by VASILESCU et al [11]. The frequency of DF508 homozygous, DF508 heterozygous and non-DF508 CF patients did not differ significantly between HA and Ha carriers.…”

Section: Discussionsupporting

confidence: 65%

“…Based on a high variability in CXCR1 and CXCR2 mRNA and protein expression ( fig. 1a and b and data not shown), we set out to assess whether genetic hot-spots within the CXCR1 and CXCR2 genes [11] associate with CXCR1/2 expression levels and CF lung disease severity in a well-characterised CF patient cohort (table 1). 191 CF patients were homozygous for DF508, 129 were heterozygous carriers of the DF508 allele of CFTR, and 122 had CFTR mutations other than DF508.…”

Section: Resultsmentioning

confidence: 99%

“…Polymorphisms with a minor allele frequency .1% were selected based on the mutation screening performed by VASILESCU et al [11] and genotyped in the aforementioned CF population to investigate the influence of SNPs on CF lung disease. Genomic DNA was extracted from whole blood by a standard salting-out method and DNA samples were genotyped using matrix-assisted laser desorption/ionisation timeof-flight mass spectrometry (Sequenom, San Diego, CA, USA), as described in detail previously [12].…”

Section: Cxcr1/cxcr2 Genotypingmentioning

confidence: 99%

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CXCR1andCXCR2haplotypes synergistically modulate cystic fibrosis lung disease

Kormann

Hector²,

Marcos³

et al. 2011

Eur Respir J

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Cystic fibrosis (CF) lung disease severity is largely independent on the CF transmembrane conductance regulator (CFTR) genotype, indicating the contribution of genetic modifiers. The chemokine receptors CXCR1 and CXCR2 have been found to play essential roles in the pathogenesis of CF lung disease. Here, we determine whether genetic variation of CXCR1 and CXCR2 influences CF lung disease severity.Genomic DNA of CF patients in Germany (n5442) was analysed for common variations in CXCR1 and CXCR2 using a single-nucleotide polymorphism (SNP) tagging approach. Associations of CXCR1 and CXCR2 SNPs and haplotypes with CF lung disease severity, CXCR1 and CXCR2 expression, and neutrophil effector functions were assessed.Four SNPs in CXCR1 and three in CXCR2 strongly correlated with age-adjusted lung function in CF patients. SNPs comprising haplotypes CXCR1_Ha and CXCR2_Ha were in high linkage disequilibrium and patients heterozygous for the CXCR1-2 haplotype cluster (CXCR1-2_Ha) had lower lung function compared with patients with homozygous wild-type alleles (forced expiratory volume in 1 s f70% predicted, OR 7.24; ). CF patients carrying CXCR1-2_Ha showed decreased CXCR1 combined with increased CXCR2 mRNA and protein expression, and displayed disturbed antibacterial effector functions.CXCR1 and CXCR2 genotypes modulate lung function and antibacterial host defence in CF lung disease.

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Section: Discussionsupporting

confidence: 65%

Section: Resultsmentioning

confidence: 99%

Section: Cxcr1/cxcr2 Genotypingmentioning

confidence: 99%

See 1 more Smart Citation

CXCR1andCXCR2haplotypes synergistically modulate cystic fibrosis lung disease

Kormann

Hector²,

Marcos³

et al. 2011

Eur Respir J

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“…Notably, upregulation of CCL23 was observed with HIV-1/P 4 -treated cells, which have not been shown previously in the context of HIV-1 infection. Upregulation of other pro-inflammatory cytokines, such as XCR1 supports HIV-1 replication (Vasilescu et al 2007), and IL-36β is indicative of the activation of the MAPK and NF-κB pathway (Tripodi et al 2012). These results suggest that P 4 induces pro-inflammatory responses for HIV-1 infection (Fig.…”

Section: Discussionmentioning

confidence: 99%

Progesterone augments cell susceptibility to HIV-1 and HIV-1/HSV-2 co-infections

Ragupathy

Wang

Tan

et al. 2016

Journal of Molecular Endocrinology

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In human immunodeficiency virus type 1 (HIV-1)-infected women, oral or injectable progesterone containing contraceptive pills may enhance HIV-1 acquisition in vivo, and the mechanism by which this occurs is not fully understood. In developing countries, Herpes simplex virus type-2 (HSV-2) co-infection has been shown to be a risk for increase of HIV-1 acquisition and, if co-infected women use progesterone pills, infections may increase several fold. In this study, we used an in vitro cell culture system to study the effects of progesterone on HIV-1 replication and to explore the molecular mechanism of progesterone effects on infected cells. In our in vitro model, CEMss cells (lymphoblastoid cell line) were infected with either HIV-1 alone or co-infected with HSV-2. HIV-1 viral load was measured with and without sex hormone treatment. Progesterone-treated cells showed an increase in HIV-1 viral load (1411.2 pg/mL) compared with cells without progesterone treatment (993.1 pg/mL). Increased cell death was noted with HSV-2 co-infection and in progesterone-treated cells. Similar observations were noted in peripheral blood mononuclear cells (PBMC) cells derived from three female donors. Progesterone-treated cells also showed reduced antiviral efficacy. Inflammatory cytokines and associations with biomarkers of disease progression were explored. Progesterone upregulated inflammatory cytokines and chemokines conversely and downregulated anti-apoptotic Bcl-2 expression. Nuclear protein analysis by electrophoretic mobility shift assay showed the association of progesterone with progesterone response element (PRE), which may lead to downregulation of Bcl-2. These data indicate that progesterone treatment enhances HIV-1 replication in infected cells and co-infection with HSV-2 may further fuel this process.

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“…CXCR1 and CXCR2 genes are located o chromosome 2q35 and several polymorphisms have been described including SNPs T92G (CXCR1 -300) and C1003T (CXCR1-142) that result in a CXCR1 haplotype Ha. A genetic study on French cohort composing of rapid and slow progressors HIV-1 infected individual identified a strong association of CXCR1 haplotype Ha with protection against rapid progression to AIDS (Vasilescu et al, 2007). It was suggested that the inhibitory effect of CXCR1 Ha could be mediated by suppressing CD4 + and CXCR4 expression (Kaur & Mehra, 2009).…”

Section: Cxcr1 Cxcr2mentioning

confidence: 99%

The Role of Genetic Polymorphisms in the Chemokine and their Receptors and Cytokines in the Human Immunodeficiency Virus Type 1 (HIV-1) Infection

Reiche¹,

Amarante²,

Watanabe³

2011

HIV and AIDS - Updates on Biology, Immunology, Epidemiology and Treatment Strategies

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A haplotype of the human CXCR1 gene protective against rapid disease progression in HIV-1⁺patients

Cited by 26 publications

References 31 publications

CXCR1andCXCR2haplotypes synergistically modulate cystic fibrosis lung disease

CXCR1andCXCR2haplotypes synergistically modulate cystic fibrosis lung disease

Progesterone augments cell susceptibility to HIV-1 and HIV-1/HSV-2 co-infections

The Role of Genetic Polymorphisms in the Chemokine and their Receptors and Cytokines in the Human Immunodeficiency Virus Type 1 (HIV-1) Infection

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A haplotype of the human CXCR1 gene protective against rapid disease progression in HIV-1+patients

Cited by 26 publications

References 31 publications

CXCR1andCXCR2haplotypes synergistically modulate cystic fibrosis lung disease

CXCR1andCXCR2haplotypes synergistically modulate cystic fibrosis lung disease

Progesterone augments cell susceptibility to HIV-1 and HIV-1/HSV-2 co-infections

The Role of Genetic Polymorphisms in the Chemokine and their Receptors and Cytokines in the Human Immunodeficiency Virus Type 1 (HIV-1) Infection

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A haplotype of the human CXCR1 gene protective against rapid disease progression in HIV-1⁺patients