40 research outputs found

    Characterization of Reemerging Chikungunya Virus

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    An unprecedented epidemic of chikungunya virus (CHIKV) infection recently started in countries of the Indian Ocean area, causing an acute and painful syndrome with strong fever, asthenia, skin rash, polyarthritis, and lethal cases of encephalitis. The basis for chikungunya disease and the tropism of CHIKV remain unknown. Here, we describe the replication characteristics of recent clinical CHIKV strains. Human epithelial and endothelial cells, primary fibroblasts and, to a lesser extent, monocyte-derived macrophages, were susceptible to infection and allowed viral production. In contrast, CHIKV did not replicate in lymphoid and monocytoid cell lines, primary lymphocytes and monocytes, or monocyte-derived dendritic cells. CHIKV replication was cytopathic and associated with an induction of apoptosis in infected cells. Chloroquine, bafilomycin-A1, and short hairpin RNAs against dynamin-2 inhibited viral production, indicating that viral entry occurs through pH-dependent endocytosis. CHIKV was highly sensitive to the antiviral activity of type I and II interferons. These results provide a general insight into the interaction between CHIKV and its mammalian host

    Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

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    Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

    A Prophage in Diabetic Foot Ulcer–Colonizing Staphylococcus aureus Impairs Invasiveness by Limiting Intracellular Growth

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    International audienceThe mechanisms that drive the transition from commensality to invasiveness in Staphylococcus aureus are poorly understood. We recently reported that >50% of S. aureus isolates from uninfected diabetic foot ulcers in French patients harbor a prophage, ROSA-like, that is absent from invasive isolates from diabetic foot infections, including osteomyelitis. Here we show that the ROSA-like insertion abolishes the ability of S. aureus to replicate within osteoblasts, the bone-forming cells, greatly reducing damage to infected cells. These results unravel an important mechanism by which particular S. aureus strains are maintained in a commensal state in diabetic foot ulcers

    Mupirocin Resistance in Isolates of Staphylococcus spp. from Nasal Swabs in a Tertiary Hospital in France

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    International audienceMupirocin is a topical antibiotic largely used to eradicate staphylococcal nasal carriage. Here, we investigated the prevalence of mupirocin-resistant Staphylococcus aureus and coagulase-negative staphylococcal isolates recovered from patients in different wards in a hospital (Lyon, France), which were determined both phenotypically with an Epsilometer test (Etest) and genetically by PCR for mupA and mupB

    Evaluation of a commercial immunochromatographic assay for rapid routine identification of PBP2a-positive Staphylococcus aureus and coagulase-negative staphylococci

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    International audienceWe evaluated the performance of an immunochromatographic assay (PBP2a Culture Colony Test - Alere\texttrademark), detecting protein-binding penicillin 2a on staphylococci primary isolates in only 6minutes. The assay is highly sensitive for the direct detection of MRSA on various culture media whereas it requires cefoxitin induction for methicillin-resistant coagulase-negative staphylococci

    Xynthia : leçons d'une catastrophe

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    International audienceThe storm Xynthia occurred on the 28th of february 2010. It has been one of the most deadly seen on the French territory since several decades, with 47 victims, half of them found on the department of VendĂ©e. We suggest a global interpretation of the reasons of the disaster on two adjoining districts, in the south of this department, La Faute-sur-mer and L'Aiguillon-sur-mer. We first focus on the different natural hazard's characteristics: wind's strength, role of the high tide's coefficients, topography of the affected coastal areas, particularly on enclosed bays and estuaries, constitute risk factors which have add their effects in time and space, creating strong uplifts of sea level. We then analyse the crisis development, which partially explains the vulnerability of specific areas. Following, the first economic consequences on submerged lands are presented. Finally, we point the lack of risk assessment, resulting from long and carelessness practices on territorial management, to the detriment of natural processes knowledge and constraints, especially on potentially submerged areas. The lack of risk awareness has persisted with decisions taken locally, as well as at the highest national politic power.La tempĂȘte Xynthia, survenue le 28 fĂ©vrier 2010, a Ă©tĂ© l'une des plus meurtriĂšres qu'ait connu le territoire français mĂ©tropolitain depuis plusieurs dĂ©cennies, avec 47 victimes, dont plus de la moitiĂ© sur le seul dĂ©partement de la VendĂ©e. Nous proposons une interprĂ©tation globale des raisons de la catastrophe sur deux communes contigĂŒes particuliĂšrement touchĂ©es du sud-vendĂ©en, La Faute-sur mer et l'Aiguillon-sur-mer. Nous nous intĂ©ressons d'abord Ă  caractĂ©riser les diffĂ©rents Ă©lĂ©ments composant l'alĂ©a : force des vents, rĂŽle jouĂ© par les forts coefficients de marĂ©e, topographie des espaces littoraux et effets de sites de fond de baie ou d'estuaire constituent des facteurs qui ont cumulĂ© leurs effets dans le temps et l'espace, gĂ©nĂ©rant ainsi de trĂšs fortes surcotes. Nous revenons ensuite sur le dĂ©roulement de la crise, qui permet une premiĂšre identification des secteurs et des causes de vulnĂ©rabilitĂ©, puis sur les premiĂšres consĂ©quences Ă©conomiques des submersions marines. Enfin, nous rĂ©pertorions les Ă©lĂ©ments permettant de conclure Ă  une apprĂ©hension du risque dĂ©faillante, expliquant l'enchaĂźnement dans le temps long d'imprudences et de nĂ©gligences ayant pris le pas sur une occupation de l'espace tenant compte des particularitĂ©s des sites submergĂ©s. Cette absence de culture du risque a ensuite Ă©tĂ© aggravĂ©e par des dĂ©cisions post-crise prises soit localement, soit au plus haut niveau de l'Etat
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