Éditeur(s) : HAL CCSD
Résumé : International audience
Antiviral proteins that recognize pathogen-specific or aberrantly located molecular motifs are perfectly positioned to act as pattern-recognition receptors and signal to the immune system. Here we investigated whether the interferon-induced viral restriction factor tetherin (CD317/BST2), which is known to inhibit HIV-1 particle release by physically tethering virions to the cell surface, has such a signaling role. We find that upon restriction of Vpu-defective HIV-1, tetherin acts as a virus sensor to induce NFκB-dependent proinflammatory gene expression. Signaling requires both tetherin's extracellular domain involved in virion retention and determinants in the cytoplasmic tail, including an endocytic motif, although signaling is independent of virion endocytosis. Furthermore, recruitment of the TNF-receptor-associated factor TRAF6 and activation of the mitogen-activated protein kinase TAK1 are critical for signaling. Human tetherin's ability to mediate efficient signaling may have arisen as a result of a five amino acid deletion that occurred in hominids after their divergence from chimpanzees.
ISSN: 1934-6069

hal-01121777
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01121777
PUBMED : 23159053
DOI : 10.1016/j.chom.2012.10.007
PUBMEDCENTRAL : PMC3556742

Éditeur(s) : HAL CCSD
Résumé : International audience
Background: Comparative analysis, which aims at investigating ecological and evolutionary patterns among species, may help at targeting reservoirs of zoonotic diseases particularly in countries presenting high biodiversity. Here, we developed a simple method to target rodent reservoirs using published studies screening microparasite infections. Methods: We compiled surveys of microparasites investigated in rodents trapped in Thailand. The data comprise a total of 17,358 rodents from 18 species that have been investigated for a total of 10 microparasites (viruses, bacteria and protozoans). We used residual variation of microparasite richness controlled for both rodent sample size and pathogens' screening effort to identify major rodent reservoirs and potential risky habitats. Results: Microparasite species richness was positively related to rodent sample size and pathogens' screening effort. The investigation of the residual variations of microparasite species richness showed that several rodent species harboured more pathogens than expected by the regression model. Similarly, higher pathogen richness than expected was observed in rodents living in non-flooded lands, forests and paddy fields. Conclusion: Our results suggest to target some rodent species that are not commonly investigated for pathogen screening or surveillance such as R. andamanensis or B. savilei, and that non-flooded lands and forests should be more taken into caution, whereas much surveys focused on paddy rice fields and households.
Infection Ecology and Epidemiology

ird-00714369
http://hal.ird.fr/ird-00714369
http://hal.ird.fr/ird-00714369v2/document
DOI : 10.3402/iee.v2iO.18637
IRD : fdi:010055557

Éditeur(s) : HAL CCSD SAGE Publications
Résumé : International audience
In Western French Guiana there was a dramatic increase in HIV-prevalence between 1990 and 2000. The present study describes the causes of fever among HIV patients hospitalized in the medical ward of the only hospital in the western part of French Guiana. A retrospective descriptive study was conducted between January 1st 2008 and June 30th 2010 in the department of medicine of Saint Laurent du Maroni Hospital. The main characteristics of 67 patients having presented with fever in the first 48 hours of hospitalization were described. Among patients with CD4<200/mm3 the main febrile opportunistic infection was disseminated histoplasmosis (41.1%). Among patients with CD4 counts <50/mm3 and fever without focal points 85.7% had disseminated histoplasmosis. Three patients died and all had disseminated histoplasmosis. Disseminated histoplasmosis is the most common febrile opportunistic infection in western French Guiana. Primary prophylaxis with itraconazole among immunocompromised patients seems warranted.
ISSN: 0956-4624

inserm-01082409
http://www.hal.inserm.fr/inserm-01082409
http://www.hal.inserm.fr/inserm-01082409/document
http://www.hal.inserm.fr/inserm-01082409/file/2014%2C%20Vantilcke%20-%20Fever%20and%20HIV.pdf
http://www.hal.inserm.fr/inserm-01082409/file/Histoplasmosis_tab_2%5B1%5D%20revised.pdf

Éditeur(s) : HAL CCSD Wiley Open Access
Résumé : International audience
Estetrol (E4) is a natural estrogen with a long half-life produced only by the human fetal liver during pregnancy. The crystal structures of the estrogen receptor α (ERα) ligand-binding domain bound to 17β-estradiol (E2) and E4 are very similar, as well as their capacity to activate the two activation functions AF-1 and AF-2 and to recruit the coactivator SRC3. In vivo administration of high doses of E4 stimulated uterine gene expression, epithelial proliferation, and prevented atheroma, three recognized nuclear ERα actions. However, E4 failed to promote endothelial NO synthase activation and acceleration of endothelial healing, two processes clearly dependent on membrane-initiated steroid signaling (MISS). Furthermore, E4 antagonized E2 MISS-dependent effects in endothelium but also in MCF-7 breast cancer cell line. This profile of ERα activation by E4, uncoupling nuclear and membrane activation, characterizes E4 as a selective ER modulator which could have medical applications that should now be considered further.
ISSN: 1757-4676

hal-01118028
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01118028
PUBMED : 25214462
PUBMEDCENTRAL : PMC4287935
DOI : 10.15252/emmm.201404112

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The mycotoxin enniatin B (EnnB) is predominantly produced by species of the Fusarium genera, and often found in grain. The cytotoxic effect of EnnB has been suggested to be related to its ability to form ionophores in cell membranes. The present study examines the effects of EnnB on cell death, differentiation, proliferation and pro-inflammatory responses in the murine monocyte-macrophage cell line RAW 264.7. Exposure to EnnB for 24 h caused an accumulation of cells in the G0/G1-phase with a corresponding decrease in cyclin D1. This cell cycle-arrest was possibly also linked to the reduced cellular ability to capture and internalize receptors as illustrated by the lipid marker ganglioside GM1. EnnB also increased the number of apoptotic, early apoptotic and necrotic cells, as well as cells with elongated spindle-like morphology. The Neutral Red assay indicated that EnnB induced lysosomal damage; supported by transmission electron microscopy (TEM) showing accumulation of lipids inside the lysosomes forming lamellar structures/myelin bodies. Enhanced levels of activated caspase-1 were observed after EnnB exposure and the caspase-1 specific inhibitor ZYVAD-FMK reduced EnnB-induced apoptosis. Moreover, EnnB increased the release of interleukin-1 beta (IL-1β) in cells primed with lipopolysaccharide (LPS), and this response was reduced by both ZYVAD-FMK and the cathepsin B inhibitor CA-074Me. In conclusion, EnnB was found to induce cell cycle arrest, cell death and inflammation. Caspase-1 appeared to be involved in the apoptosis and release of IL-1β and possibly activation of the inflammasome through lysosomal damage and leakage of cathepsin B.
ISSN: 0041-008X

inserm-00871698
http://www.hal.inserm.fr/inserm-00871698
DOI : 10.1016/j.taap.2012.03.014
PUBMED : 22483798